Gene Detail

Gene Symbol EGFR
Synonyms ERBB | ERBB1 | HER1 | mENA | NISBD2 | PIG61
Gene Description EGFR (HER1), epidermal growth factor receptor, is a tyrosine kinase receptor, which activates RAS/RAF/MEK and PI3K/AKT/mTOR pathways, leading to increased cell proliferation and growth (PMID: 24312144). EGFR activating mutations, amplification, and overexpression are found in a variety of tumor tumors, including non-small cell lung cancer (PMID: 26609494, PMID: 30284706) and colorectal cancer (PMID: 30243897), and the EGFRvIII variant is commonly found in glioblastoma (PMID: 30201736).
Entrez Id 1956
Chromosome 7
Map Location 7p11.2
Canonical Transcript NM_005228

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
V786M missense unknown EGFR V786M lies within the protein kinase domain of the Egfr protein (UniProt.org). V786M has been identified in the scientific literature (PMID: 18379371, PMID: 24406864), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
G724S missense gain of function EGFR G724S lies within the protein kinase domain of the Egfr protein (UniProt.org). G724S results in constitutive phosphorylation of Egfr and is transforming in cell culture (PMID: 24894453).
E734K missense unknown EGFR E734K lies within the protein kinase domain of the Egfr protein (UniProt.org). E734K has been identified in the scientific literature (PMID: 16533793, PMID: 19648884, PMID: 26725423), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
P1202Q missense unknown EGFR P1202Q lies within the cytoplasmic domain of the Egfr protein (UniProt.org). P1202Q has not been characterized in the scientific literature and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
V774M missense unknown EGFR V774M lies within the protein kinase domain of the Egfr protein (UniProt.org). V774M has been identified in the scientific literature (PMID: 27123274, PMID: 17409930, PMID: 29858019), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
H870R missense gain of function EGFR H870R lies within the protein kinase domain of the Egfr protein (UniProt.org). H870R results in constitutive phosphorylation of Egfr, activation of downstream signaling in cell culture (PMID: 19671738), and induces cell proliferation and cell viability in culture (PMID: 29533785).
D770_N771insNPY insertion gain of function - predicted EGFR D770_N771insNPY results in the insertion of three amino acids in the protein kinase domain of the Egfr protein between amino acids 770 and 771 (UniProt.org). D770_N771insNPY results in increased Egfr kinase activity and is transforming in culture (PMID: 24353160).
E746_T751delinsA indel unknown EGFR E746_T751delinsA results in a deletion of six amino acids in the protein kinase domain of the Egfr protein from aa 746 to aa 751, combined with the insertion of an alanine (A) at the same site (UniProt.org). E746_T751delinsA results in increased transformation ability in one of two different cell lines in one study (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
E734Q missense gain of function - predicted EGFR E734Q lies within the protein kinase domain of the Egfr protein (UniProt.org). E734Q results in increased transformation ability in two different cell lines in one study (PMID: 29533785) and therefore, is predicted to lead to a gain of Egfr protein function.
V769M missense gain of function - predicted EGFR V769M lies within the protein kinase domain of the Egfr protein (UniProt.org). V769M results in increased downstream signaling in cell culture in one study (JCO Precision Oncology 2017, 1:1-10) and therefore, is predicted to result in a gain of Egfr protein function.
S921R missense unknown EGFR S921R lies within the protein kinase domain of the Egfr protein (UniProt.org). S921R has not been characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
D191N missense no effect - predicted EGFR D191N lies within the extracellular domain of the Egfr protein (UniProt.org). D191N results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
D612N missense no effect - predicted EGFR D612N does not lie within known domains of the Egfr protein (UniProt.org). D612N results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
D994Y missense unknown EGFR D994Y lies within the cytoplasmic domain of the Egfr protein (UniProt.org). D994Y has not been characterized in the scientific literature and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
act mut unknown gain of function EGFR act mut indicates that this variant results in a gain of function in the Egfr protein. However, the specific amino acid change has not been identified.
EGFR - YAP1 fusion unknown EGFR-YAP1 results from the fusion of EGFR and YAP1 (PMID: 31064887). EGFR-YAP1 has been identified in lung adenocarcinoma (PMID: 31064887), but has not been biochemically characterized and therefore, the effect on fusion protein function is unknown (PubMed, Jun 2019).
E967A missense unknown EGFR E967A lies within the protein kinase domain of the Egfr protein (UniProt.org). E967A results in increased transformation ability in one of two different cell lines in one study (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
L633F missense no effect - predicted EGFR L633F lies within the extracellular domain of the Egfr protein (UniProt.org). L633F results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
E746_T751delinsV indel gain of function - predicted EGFR E746_T751delinsV results in a deletion of six amino acids in the protein kinase domain of the Egfr protein from aa 746 to aa 751, combined with the insertion of a valine (V) at the same site (UniProt.org). E746_T751delinsV has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other EGFR exon 19 deletion and deletion-insertion mutations (PMID: 19147750, PMID: 22190593, PMID: 23387505).
R108G missense gain of function - predicted EGFR R108G lies within the extracellular domain of the Egfr protein (UniProt.org). R108G results in increased transformation ability in two different cell lines in one study (PMID: 29533785) and therefore, is predicted to lead to a gain of Egfr protein function.
V769_D770insMASVD insertion gain of function - predicted EGFR V769_D770insMASVD results in the insertion of five amino acids in the protein kinase domain of the Egfr protein between amino acids 769 and 770 (UniProt.org). V769_D770insMASVD has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other Egfr exon 20 insertions (PMID: 24353160).
E690K missense no effect - predicted EGFR E690K lies within the cytoplasmic domain of the Egfr protein (UniProt.org). E690K results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
L861F missense unknown EGFR L861F lies within the protein kinase domain of the Egfr protein (UniProt.org). L861F has been identified in the scientific literature (PMID: 19536777, PMID: 23945384), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
Y125C missense unknown EGFR Y125C lies within the extracellular domain of the Egfr protein (UniProt.org). Y125C has been identified in sequencing studies (PMID: 23788652), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
D956V missense no effect - predicted EGFR D956V lies within the protein kinase domain of the Egfr protein (UniProt.org). D956V does not induce cell proliferation in the abscence of IL-3, similar to wild-type Egfr, and therefore, is predicted to have no effect on Egfr protein function (PMID: 30952700).
exon 19 ins insertion gain of function EGFR exon 19 insertions are in-frame insertions within the kinase domain of Egfr (PMID: 22190593). Exon 19 insertions result in increased Egfr kinase activity and cell transformation in culture, and are associated with sensitivity to Egfr tyrosine kinase inhibitors (PMID: 22190593).
G721A missense unknown EGFR G721A lies within the protein kinase domain of the Egfr protein (UniProt.org). G721A has been identified in the scientific literature (PMID: 27121209), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
T854A missense unknown EGFR T854A lies within the protein kinase domain of the Egfr protein (UniProt.org). T854A has been associated with drug resistance (PMID: 19010870), and results in increased cell proliferation and cell viability as compared to wild-type Egfr in one of two cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown. Y
E709K missense gain of function EGFR E709K lies within the cytoplasmic domain of the Egfr protein (UniProt.org). E709K confers a gain of function to Egfr, as indicated by increased Egfr phosphorylation in patient samples and is transforming in cell culture (PMID: 19726454, PMID: 29533785).
G796S missense gain of function EGFR G796S lies within the protein kinase domain of the Egfr protein (UniProt.org). G796S results in constitutive activation of Egfr, increased downstream signaling, and leads to increased proliferation, invasion, and transformation of cultured cells (PMID: 18193092, PMID: 29533785).
G874S missense unknown EGFR G874S lies within the protein kinase domain of the Egfr protein (UniProt.org). G874S has been identified in the scientific literature (PMID: 18176089, PMID: 25343854, PMID: 26773740), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
T302H missense unknown EGFR T302H lies within the extracellular domain of the Egfr protein (UniProt.org). T302H has been identified in sequencing studies (PMID: 30555633), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Jun 2019).
A871V missense unknown EGFR A871V lies within the protein kinase domain of the Egfr protein (UniProt.org). A871V has been identified in the scientific literature (PMID: 16152581, PMID: 19060236, PMID: 26773740), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
Q1159R missense unknown EGFR Q1159R lies within the cytoplasmic domain of the Egfr protein (UniProt.org). Q1159R demonstrates greater than 24.5-fold growth advantage in IL-3-depeleted cells in culture, as compared to wild-type Egfr (PMID: 30952700), but the assay has not been validated and therefore, the functional effect of Q1159R on Egfr protein function is unknown.
V738G missense unknown EGFR V738G lies within the protein kinase domain of the Egfr protein (UniProt.org). V738G has been identified in sequencing studies (PMID: 18302229), but not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
K806E missense unknown EGFR K806E lies within the protein kinase domain of the Egfr protein (UniProt.org). K806E has been identified in the scientific literature (PMID: 18676761, PMID: 16870303), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
S198R missense no effect - predicted EGFR S198R lies within the extracellular domain of the Egfr protein (UniProt.org). S198R results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
G719fs frameshift loss of function - predicted EGFR G719fs results in a change in the amino acid sequence of the Egfr protein beginning at aa 719 of 1210, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), G719fs is predicted to lead to a loss of Egfr protein function.
I941R missense loss of function EGFR I941R lies within the protein kinase domain of the Egfr protein (UniProt.org). I941R confers a loss of function on the Egfr protein as indicated by disruption of dimerization in culture (PMID: 24063894, PMID: 24894453).
A871G missense gain of function EGFR A871G lies within the protein kinase domain of the Egfr protein (UniProt.org). A871G results in increased Egfr activity and upregulation of heat shock proteins expression in cell culture (PMID: 26146591).
G873Q missense unknown EGFR G873Q lies within the protein kinase domain of the Egfr protein (UniProt.org). G873Q has not been characterized in the scientific literature and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
P281T missense unknown EGFR P281T lies within the extracellular domain of the Egfr protein (UniProt.org). P281T has been identified in the scientific literature (PMID: 27034166) , but has not been biochemically characterized and therefore, its effect of Egfr protein function is unknown (PubMed, Feb 2019).
P959fs frameshift unknown EGFR P959fs results in a change in the amino acid sequence of the Egfr protein beginning at aa 959 of 1210, likely resulting in premature truncation of the functional protein (UniProt.org). P959fs has not been characterized in the scientific literature and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
R776C missense gain of function EGFR R776C lies within the protein kinase domain of the Egfr protein (UniProt.org). R776C results in constitutive phosphorylation of Egfr, increased downstream signaling, and is transforming in cell culture (PMID: 19147750, PMID: 29533785).
fusion fusion unknown EGFR fusion indicates a fusion of the EGFR gene, but the fusion partner is unknown.
K728* missense unknown EGFR K728* results in a premature truncation of the Egfr protein at amino acid 728 of 1210 (UniProt.org). The functional effect of K261* is conflicting, as K728* demonstrates greater than 24.5-fold growth advantage in IL-3-depeleted cells in culture, as compared to wild-type Egfr (PMID: 30952700), however loss of a majority of the protein kinase domain including the C-terminal portion of the ATP binding site (UniProt.org) predicts a loss of function on the Egfr protein.
S116F missense no effect - predicted EGFR S116F lies within the extracellular domain of the Egfr protein (UniProt.org). S116F results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
D770_N771insAPW insertion gain of function - predicted EGFR D770_N771insAPW results in the insertion of three amino acids in the protein kinase domain of the Egfr protein between amino acids 770 and 771 (UniProt.org). D770_N771insAPW has not been biochemically characterized, but is predicted to lead to a gain of function based on the effect of other Egfr exon 20 insertions (PMID: 24353160).
G598A missense no effect - predicted EGFR G598A lies within the extracellular domain of the Egfr protein (UniProt.org). G598A results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
D1014V missense unknown EGFR D1014V lies within the cytoplasmic domain of the Egfr protein (UniProt.org). D1014V has not been characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
M178I missense unknown EGFR M178I lies within the extracellular domain of the Egfr protein (UniProt.org). M178I results in increased cell proliferation and cell viability as compared to wild-type Egfr in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown.
P589L missense unknown EGFR P589L lies within the extracellular domain of the Egfr protein (UniProt.org). P589L results in increased cell proliferation and cell viability as compared to wild-type Egfr in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown.
I821T missense unknown EGFR I821T lies within the protein kinase domain of the Egfr protein (UniProt.org). I821T has been identified in the scientific literature (PMID: 26046796), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
EGFR - ZNF713 fusion unknown EGFR-ZNF713 results from the fusion of EGFR and ZNF713 (PMID: 31064887). EGFR-ZNF713 has been identified in lung adenocarcinoma (PMID: 31064887), but has not been biochemically characterized and therefore, the effect on fusion protein function is unknown (PubMed, Jun 2019).
E746_T751del deletion gain of function - predicted EGFR E746_T751del results in the deletion of six amino acids in the protein kinase domain of the Egfr protein from amino acids 746 to 751 (UniProt.org). E746_T751del has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other EGFR exon 19 deletion mutations (PMID: 16373402, PMID: 16912195, PMID: 23387505).
T34_A289del deletion gain of function EGFR T34_A289del results in the deletion of 256 amino acids in the extracellular domain of the Egfr protein from amino acids 34 to 289 (UniProt.org). T34_A289del results in ligand independent constitutive phosphorylation of Egfr, increased proliferation, and invasion of cells in culture (PMID: 27216155).
P794L missense unknown EGFR P794L lies within the protein kinase domain of the Egfr protein (UniProt.org). P794L has been associated with resistance to Tagrisso (osimertinib) in a patient (PMID: 29704676), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019). Y
G796R missense unknown EGFR G796R lies within the protein kinase domain of the Egfr protein (UniProt.org). G796R has been demonstrated to occur as a secondary drug resistance mutation (PMID: 29857056), but has not been biochemically characterized and therefore, it's effect on Egfr protein function is unknown (PubMed, Jan 2019). Y
amp none no effect EGFR amp indicates an increased number of copies of the EGFR gene. However, the mechanism causing the increase is unspecified.
D770_N771insGF insertion gain of function - predicted EGFR D770_N771insGF results in the insertion of two amino acids in the protein kinase domain of the Egfr protein between amino acids 770 and 771 (UniProt.org). D770_N771insGF has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other Egfr exon 20 insertions (PMID: 24353160).
G42D missense no effect - predicted EGFR G42D lies within the extracellular domain of the Egfr protein (UniProt.org). G42D results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
V851I missense unknown EGFR V851I lies within the protein kinase domain of the Egfr protein (UniProt.org). V851I has been demonstrated to confer resistance to Egfr inhibitors (PMID: 16152581, PMID: 15870435, PMID: 29141884), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019). Y
K721M missense loss of function EGFR K721M lies within the protein kinase domain of the post-translationally processed Egfr protein, and corresponds to K745M in the canonical form (PMID: 20495563, UniProt.org). K721M results in a loss of Egfr kinase activity in cultured cells (PMID: 3498122, PMID: 19560417).
F48Y missense unknown EGFR F48Y lies within the extracellular domain of the Egfr protein (UniProt.org). F48Y demonstrates greater than 24.5-fold growth advantage in IL-3-depeleted cells in culture, as compared to wild-type Egfr (PMID: 30952700), but the assay has not been validated and therefore, the functional effect of F48Y on Egfr protein function is unknown.
R451C missense loss of function - predicted EGFR R451C lies within the extracellular domain of the Egfr protein (UniProt.org). R451C results in reduced Egfr affinity for Egf binding in cell culture in one study (PMID: 26843189) and therefore, is predicted to lead to a loss of Egfr protein function.
H850Y missense unknown EGFR H850Y lies within the protein kinase domain of the Egfr protein (UniProt.org). H850Y has been identified in the scientific literature (PMID: 22426987), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
E746K missense gain of function EGFR E746K lies within the protein kinase domain of the Egfr protein (UniProt.org). E746K confers a gain of function to the Egfr protein as demonstrated by increased autophosphorylation and downstream signaling in cell culture (PMID: 24743239).
D761Y missense unknown EGFR D761Y lies within the protein kinase domain of the Egfr protein (UniProt.org). D761Y has been identified in the scientific literature (PMID: 17085664), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Apr 2019). Y
L747_A755delinsSRD indel gain of function - predicted EGFR L747_A755delinsSRD results in a deletion of nine amino acids in the protein kinase domain of the Egfr protein from aa 747 to aa 755, combined with the insertion of three amino acids at the same site (UniProt.org). L747_A755delinsSRD has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other EGFR exon 19 deletion and deletion-insertion mutations (PMID: 19147750, PMID: 22190593, PMID: 23387505).
A216T missense unknown EGFR A216T lies within the extracellular domain of the Egfr protein (UniProt.org). A216T has been identified in the scientific literature (PMID: 29141884), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
G857E missense unknown EGFR G857E lies within the protein kinase domain of the Egfr protein (UniProt.org). G857E has been identified in the scientific literature (PMID: 19238633, PMID: 23139256, PMID: 25435280), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
L747_T751del deletion gain of function EGFR L747_T751del results in the deletion of five amino acids in the protein kinase domain of the Egfr protein from amino acids 747 to 751 (UniProt.org). L747_T751del results in increased Egfr kinase activity (PMID: 23387505) and and demonstrates increased transformation ability in two different cell lines in culture (PMID: 29533785).
P1059R missense no effect - predicted EGFR P1059R lies within the cytoplasmic domain of the Egfr protein (UniProt.org). P1059R results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
T263I missense unknown EGFR T263I lies within the extracellular domain of the Egfr protein (UniProt.org). T263I results in increased cell proliferation and cell viability as compared to wild-type Egfr in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown.
exon 20 ins insertion gain of function EGFR exon 20 insertions are in-frame insertions within the kinase domain of Egfr (PMID: 17318210). Exon 20 insertions result in increased Egfr kinase activity, and are associated with low sensitivity to Egfr tyrosine kinase inhibitors (PMID: 17318210, PMID: 24353160, PMID: 28363995).
V769_N771dup duplication gain of function - predicted EGFR V769_N771dup (also referred to as N771_P772insVDN) indicates the insertion of 3 duplicate amino acids, valine (V)-769 through asparagine (N)-771, in the protein kinase domain of the Egfr protein (UniProt.org). V769_N771dup has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other Egfr exon 20 insertions (PMID: 24353160).
R831C missense no effect - predicted EGFR R831C lies within the protein kinase domain of the Egfr protein (UniProt.org). R831C results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
L747_E749del deletion gain of function - predicted EGFR L747_E749del results in the deletion of three amino acids in the protein kinase domain of the Egfr protein from amino acids 747 to 749 (UniProt.org). L747_E749del has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other EGFR exon 19 deletion mutations (PMID: 16373402, PMID: 16912195, PMID: 23387505).
Q701* nonsense loss of function - predicted EGFR Q701* results in a premature truncation of the Egfr protein at amino acid 701 of 1210 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), Q701* is predicted to lead to a loss of Egfr protein function.
A237F missense unknown EGFR A237F lies within the extracellular domain of the Egfr protein (UniProt.org). A237F has been identified in sequencing studies (J Clin Oncol 37, 2019 (suppl; abstr e13000)), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Jun 2019).
T854S missense unknown EGFR T854S lies within the protein kinase domain of the Egfr protein (UniProt.org). T854S has been identified in the scientific literature (PMID: 23486275, PMID: 24376513), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
P622S missense unknown EGFR P622S lies within the extracellular domain of the Egfr protein (UniProt.org). P622S has been identified in sequencing studies (PMID: 27147599), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
V765G missense unknown EGFR V765G lies within the protein kinase domain of the Egfr protein (UniProt.org). The functional effect of V765G is conflicting, as it results in cell proliferation similar to wild-type in culture in one study (PMID: 19726454), but, in another study, demonstrates decreased cell proliferation and cell viability as compared to wild-type Egfr in one of two different cell lines in culture (PMID: 29533785), and therefore, its effect on Egfr protein function is unknown.
A767T missense gain of function - predicted EGFR A767T lies within the protein kinase domain of the Egfr protein (UniProt.org). A767T is predicted to lead to a gain of Egfr function as indicated by increased Egfr autophosphorylation in one study, and is associated with resistance to gefitinib in culture (PMID: 18497962). Y
E746_T751delinsL indel gain of function - predicted EGFR E746_T751delinsL results in a deletion of six amino acids in the protein kinase domain of the Egfr protein from aa 746 to aa 751, combined with the insertion of a leucine (L) at the same site (UniProt.org). E746_T751delinsL has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other EGFR exon 19 deletion and deletion-insertion mutations (PMID: 19147750, PMID: 22190593, PMID: 23387505).
T354K missense unknown EGFR T354K lies within the extracellular domain of the Egfr protein (UniProt.org). T354K has been identified in sequencing studies (J Clin Oncol 37, 2019 (suppl; abstr e13000)), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Jun 2019).
E804G missense gain of function EGFR E804G lies within the protein kinase domain of the Egfr protein (UniProt.org). E804G results in constitutive activation of Egfr, increased downstream signaling, increased cell proliferation and invasion, and is transforming in cell culture (PMID: 18193092, PMID: 29533785).
L747_S752del deletion gain of function - predicted EGFR L747_S752del results in the deletion of six amino acids in the protein kinase domain of the Egfr protein from amino acids 747 to 752 (UniProt.org). L747_E752del results in increased transformation ability in two different cell lines in one study (PMID: 29533785) and therefore, is predicted to lead to a gain of Egfr protein function.
F712S missense unknown EGFR F712S lies within the protein kinase domain of the Egfr protein (UniProt.org). F712S has been identified in the scientific literature (PMID: 22026926, PMID: 27121209), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
K757R missense unknown EGFR K757R lies within the protein kinase domain of the Egfr protein (UniProt.org). K757R has been identified in the scientific literature (PMID: 26773740, PMID: 23945384), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
D770_N771insGD insertion gain of function - predicted EGFR D770_N771insGD results in the insertion of two amino acids in the protein kinase domain of the Egfr protein between amino acids 770 and 771 (UniProt.org). D770_N771insGD has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other Egfr exon 20 insertions (PMID: 24353160).
L747* nonsense loss of function - predicted EGFR L747* results in a premature truncation of the Egfr protein at amino acid 747 of 1210 (UniProt.org). Due to the loss of a majority of the protein kinase domain including the C-terminal portion of the ATP binding site (UniProt.org), L747* is predicted to lead to a loss of Egfr protein function.
I744M missense unknown EGFR I744M lies within the protein kinase domain of the Egfr protein (UniProt.org). I744M has been identified in the scientific literature (PMID: 29141884, PMID: 26206728), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
K739_I744dup duplication gain of function EGFR K739_I744dup (also referred to as I744_K745insKIPVAI) indicates the insertion of six duplicate amino acids, lysine (K)-739 through isoleucine(I)-744, in the protein kinase domain of the Egfr protein (UniProt.org). K739_I744dup results in increased Egfr phosphorylation and is transforming in culture (PMID: 22190593).
K714R missense unknown EGFR K714R lies within the protein kinase domain of the Egfr protein (UniProt.org). K714R has been identified in the scientific literature (PMID: 29141884), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
S720Y missense unknown EGFR S720Y lies within the protein kinase domain of the Egfr protein (UniProt.org). S720Y has been identified in the scientific literature (PMID: 28436422), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
S380Pfs*16 frameshift loss of function - predicted EGFR S380Pfs*16 indicates a shift in the reading frame starting at amino acid 380 and terminating 16 residues downstream causing a premature truncation of the 1210 amino acid Egfr protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), S380Pfs*16 is predicted to lead to a loss of Egfr protein function.
Q52R missense unknown EGFR Q52R lies within the extracellular domain of the Egfr protein (UniProt.org). Q52R demonstrates greater than 24.5-fold growth advantage in IL-3-depeleted cells in culture, as compared to wild-type Egfr (PMID: 30952700), but the assay has not been validated and therefore, the functional effect of Q52R on Egfr protein function is unknown.
D770_N771insGV insertion gain of function - predicted EGFR D770_N771insGV results in the insertion of two amino acids in the protein kinase domain of the Egfr protein between amino acids 770 and 771 (UniProt.org). D770_N771insGV has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other Egfr exon 20 insertions (PMID: 24353160).
P596R missense unknown EGFR P596R lies within the extracellular domain of the Egfr protein (UniProt.org). P596R has been identified in the scientific literature (PMID: 23917401, PMID: 25471132), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
E746_A750del deletion gain of function EGFR E746_A750del results in the deletion of five amino acids in the kinase domain of the Egfr protein from amino acids 746 to 750 (PMID: 17318210). E746_A750del results in increased Egfr kinase activity, activation of p44/42 MAPK and AKT in cell culture, promotes tumor growth in xenograft models (PMID: 16373402, PMID: 16912195), and is transforming in cell culture (PMID: 29533785).
G810S missense gain of function EGFR G810S lies within the protein kinase domain of the Egfr protein (UniProt.org). G810S confers a gain of function on the Egfr protein as demonstrated by increased Egfr kinase activity (PMID: 19147750) and the ability to induce cell proliferation and cell viability in culture (PMID: 29533785).
exon 19 del deletion gain of function EGFR exon 19 deletions are in-frame deletions within the kinase domain of Egfr (PMID: 16912195). EGFR exon 19 deletions result in increased EGFR kinase activity and induce oncogenic transformation of cells (PMID: 16912195; PMID: 17495523).
K745_E746insTPVAIK insertion gain of function EGFR K745_E746insTPVAIK is an exon 19 mutation that results in the insertion of six amino acids in the protein kinase domain of the Egfr protein between amino acids 745 and 746 (UniProt.org). K745_E746insTPVAIK results in increased Egfr phosphorylation and is transforming in culture (PMID: 22190593).
A289T missense unknown EGFR A289T lies within the extracellular domain of the Egfr protein (PMID: 17177598). A289T increased cell proliferation and cell viability as compared to wild-type Egfr in one of two cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Apr 2019).
R831L missense unknown EGFR R831L lies within the protein kinase domain of the Egfr protein (UniProt.org). R831L has been identified in the scientific literature (PMID: 29141884), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
T751_I759del deletion gain of function - predicted EGFR T751_I759del results in the deletion of nine amino acids in the protein kinase domain of the Egfr protein from amino acids 751 to 759 (UniProt.org). T751_I759del has not been biochemically characterized, but is predicted to lead to a gain of function based on the effect of other Egfr exon 19 deletion mutations (PMID: 16373402, PMID: 23387505).
D807N missense unknown EGFR D807N lies within the protein kinase domain of the Egfr protein (UniProt.org). D807N has been identified in the scientific literature (PMID: 29312610, PMID: 21687954), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Apr 2019).
A864T missense unknown EGFR A864T lies within the protein kinase domain of the Egfr protein (UniProt.org). A864T results in Egfr autophosphorylation and activation of Akt and Erk signaling in cell culture (PMID: 19147750), however, in another study, induces similar cell proliferation and viability as wild-type Egfr in two different cell lines (PMID: 29533785), and therefore, its effect on Egfr protein function is unknown.
dec exp none no effect EGFR dec exp indicates decreased expression of the Egfr protein. However, the mechanism causing the decreased expression is unspecified.
C775Y missense unknown EGFR C775Y lies within the protein kinase domain of the Egfr protein (UniProt.org). C775Y has been identified in the scientific literature (PMID: 21087480, PMID: 26462025), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
S492R missense unknown EGFR S492R lies within the extracellular domain of the Egfr protein (UniProt.org). S492R is conflicting, as it results in similar cell growth to wild-type Egfr in vivo and in vitro (PMID: 30671888), but in another study demonstrates increased cell proliferation and viability in one of two cell lines in culture (PMID: 29533785), and has been demonstrated to confer resistance to Egfr inhibition in cell culture (PMID: 26059438), and therefore, its effect on Egfr protein function is unknown (PubMed, Apr 2019). Y
P733L missense unknown EGFR P733L lies within the protein kinase domain of the Egfr protein (UniProt.org). P733L has been identified in the scientific literature (PMID: 23605641, PMID: 27121209), but has not been biochemically characterized and and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
V834M missense unknown EGFR V834M lies within the protein kinase domain of the Egfr protein (UniProt.org). V834M has been identified in the scientific literature (PMID: 29141884), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
G863D missense no effect - predicted EGFR G863D lies within the protein kinase domain of the Egfr protein (UniProt.org). G863D results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
E709A missense gain of function EGFR E709A lies within the cytoplasmic domain of the Egfr protein (UniProt.org). E709A confers a gain of function to Egfr, as indicated by constitutive autophosphorylation, activation of downstream signaling in cell culture (PMID: 19671738), and induction of cell proliferation and cell viability in two different cell lines (PMID: 29533785).
L792F missense unknown EGFR L792F lies within the protein kinase domain of the Egfr protein (UniProt.org). L792F has been demonstrated to confer resistance to EGFR inhibitors as a secondary resistance mutation (PMID: 27913578, PMID: 28625641), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019). Y
L814P missense unknown EGFR L814P lies within the protein kinase domain of the Egfr protein (UniProt.org). L814P has been identified in the scientific literature (PMID: 16870303), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
D761G missense unknown EGFR D761G lies within the protein kinase domain of the Egfr protein (UniProt.org). D761G has been identified in sequencing studies (PMID: 18302229), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
S768T missense unknown EGFR S768T lies within the protein kinase domain of the Egfr protein (UniProt.org). S768T results in increased cell proliferation and cell viability as compared to wild-type Egfr in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown.
G465R missense gain of function EGFR G465R lies within the extracellular domain of the Egfr protein (UniProt.org). G465R results in increased Egfr phosphorylation and confers resistance to Erbitux (cetuximab) and Vectibix (panitumumab) in cell culture (PMID: 26059438, PMID: 26888827). Y
A508V missense no effect - predicted EGFR A508V lies within the extracellular domain of the Egfr protein (UniProt.org). A508V results in similar cell proliferation and autophosphorylation as wild-type Egfr in culture (PMID: 28979142) and therefore, is predicted to have no effect on Egfr protein function.
G573* nonsense loss of function - predicted EGFR G573* results in a premature truncation of the Egfr protein at amino acid 573 of 1210 (UniProt.org). Due to a loss of the protein kinase domain (UniProt.org), G573* is predicted to lead to a loss of Egfr protein function.
E758G missense unknown EGFR E758G lies within the protein kinase domain of the Egfr protein (UniProt.org). E758G has been identified in the scientific literature (PMID: 16152581), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
R776G missense gain of function EGFR R776G lies within the protein kinase domain of the Egfr protein (UniProt.org). R776G results in increased Egfr autophosphorylation in cultured cells (PMID: 21575252) and induces cell proliferation and cell viability in culture (PMID: 29533785).
M277E missense gain of function EGFR M277E lies within the extracellular domain of the Egfr protein (UniProt.org). M277E confers a gain of function to the Egfr protein, as demonstrated by in increased cell proliferation and autophosphorylation, as compared to wild-type Egfr in culture, and promotes tumor growth in mice (PMID: 28979142).
L704N missense loss of function EGFR L704N lies within the cytoplasmic domain of the Egfr protein (UniProt.org). L704N confers a loss of function on the Egfr protein as indicated by disruption of protein dimerization in culture (PMID: 24063894, PMID: 24894453).
G721D missense unknown EGFR G721D lies within the protein kinase domain of the Egfr protein (UniProt.org). G721D has not been characterized, but is predicted to be activating by structural modeling (PMID: 24817905), and therefore, its effect on Egfr protein function is unknown (PubMed, Apr 2019).
A763_Y764insFQEA insertion gain of function EGFR A763_Y764insFQEA results in the insertion of four amino acids in the C-helix region of the Egfr protein between amino acids 763 and 764 (PMID: 24353160). A763_Y764insFQEA confers a gain of function to Egfr, as indicated by increased kinase activity and is transforming in cell culture (PMID: 24353160, PMID: 29533785).
E884K missense unknown EGFR E884K lies within the protein kinase domain of the Egfr protein (UniProt.org). E884K results in constitutive phosphorylation of Egfr, increased Stat3 phosphorylation in cell culture, and leads to increased cell proliferation and differential tyrosine kinase inhibitor sensitivity in combination with EGFR L858R (PMID: 19015641), but demonstrates similar cell proliferation and viability levels as wild-type Egfr in one of two different cell lines in culture (PMID: 29533785), and therefore, its effect on Egfr protein function is unknown.
P848L missense unknown EGFR P848L lies within the protein kinase domain of the Egfr protein (UniProt.org). P848L results in lower autophosphorylation levels compared to activating mutation L858R in culture (PMID: 17877814), but demonstrates increased cell proliferation and cell viability as compared to wild-type Egfr in one of two different cell lines in culture (PMID: 29533785), and therefore, its effect on Egfr protein function is unknown.
exon20 unknown unknown EGFR exon 20 indicates an unspecified mutation has occurred in exon 20 of the EGFR gene.
G588S missense unknown EGFR G588S lies within the approximate repeat of the Egfr protein (UniProt.org). G588S results in increased transformation ability in one of two different cell lines in one study (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
L718P missense unknown EGFR L718P lies within the protein kinase domain of the Egfr protein (UniProt.org). L718P results in decreased cell proliferation and cell viability as compared to wild-type Egfr in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown.
P772_H773insPNP insertion gain of function - predicted EGFR P772_H773insPNP results in the insertion of three amino acids in the protein kinase domain of the Egfr protein between amino acids 772 and 773 (UniProt.org). P772_H773insPNP has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other Egfr exon 20 insertions (PMID: 24353160).
S752_I759del deletion gain of function - predicted EGFR S752_I759del results in the deletion of eight amino acids in the protein kinase domain of the Egfr protein from amino acids 752 to 759 (UniProt.org). S752_I759del results in increased transformation potential in cell culture in one study (PMID: 16869740) and therefore, is predicted to lead to a gain of Egfr protein function.
D770_N771insY insertion gain of function - predicted EGFR D770_N771insY results in the insertion of a tyrosine (Y) in the protein kinase domain of the Egfr protein between amino acids 770 and 771 (UniProt.org). D770_N771insY has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other Egfr exon 20 insertions (PMID: 24353160).
G983R missense gain of function - predicted EGFR G983R lies within the cytoplasmic domain of the Egfr protein (UniProt.org). G983R results in increased transformation ability in two different cell lines in one study (PMID: 29533785) and therefore, is predicted to lead to a gain of Egfr protein function.
A613T missense unknown EGFR A613T lies within the extracellular domain of the Egfr protein (UniProt.org). A613T has not been characterized in the scientific literature and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
L798I missense unknown EGFR L798I lies within the protein kinase domain of the Egfr protein (UniProt.org). L798H has been associated with resistance to Egfr tyrosine kinase inhibitors (PMID: 27283993), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Jan 2019). Y
R832H missense unknown EGFR R832H lies within the protein kinase domain of the Egfr protein (UniProt.org). R832H has been identified in the scientific literature (PMID: 26416997), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
C797G missense loss of function EGFR C797G lies within the ATP-binding pocket in the protein kinase domain of the Egfr protein (PMID: 25964297). C797G has been demonstrated to confer resistance to third-generation EGFR inhibitors (PMID: 25964297, PMID: 29807405), and results in reduced palmitoylation, loss of constitutive activation and loss of ability to form dimers upon ligand stimulation compared to wild-type EGFR as demonstrated by reduced phosphorylation of Egfr in culture (PMID: 26378037). Y
E746_P753delinsVS indel gain of function - predicted EGFR E746_P753delinsVS results in a deletion of eight amino acids in the protein kinase domain of the Egfr protein from aa 746 to aa 753, combined with the insertion of a valine (V) and a serine (S) at the same site (UniProt.org). E746_P753delinsVS has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other EGFR exon 19 deletion and deletion-insertion mutations (PMID: 19147750, PMID: 22190593, PMID: 23387505).
H773_V774insAH insertion gain of function - predicted EGFR H773_V774insAH results in the insertion of two amino acids within the drug-binding pocket in the protein kinase domain of the Egfr protein between amino acids 773 and 774 (UniProt.org, PMID: 23371856). H773_V774insAH has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other Egfr exon 20 insertion mutations (PMID: 24353160).
N771_H773dup duplication gain of function EGFR N771_H773dup (also referred to as H773_V774insNPH) indicates the insertion of 3 duplicate amino acids, asparagine (N)-771 through histidine (H)-773, in the protein kinase domain of the Egfr protein (UniProt.org). N771_H773dup results in increased cell proliferation and cell viability as compared to wild-type Egfr (PMID: 29533785), is transforming in culture, and is associated with resistance to Egfr inhibitors (PMID: 29686424). Y
G857R missense unknown EGFR G857R lies within the protein kinase domain of the Egfr protein (UniProt.org). G857R has been identified in the scientific literature (PMID: 15863375, PMID: 16857803, PMID: 19190079), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
L858R missense gain of function EGFR L858R lies within the protein kinase domain of the Egfr protein (UniProt.org). L858R results in increased kinase activity, is transforming in cell culture (PMID: 29533785, PMID: 28979142), demonstrates greater than 24.5-fold growth advantage in IL-3-depeleted cells in culture, as compared to wild-type Egfr (PMID: 30952700), and promotes tumor formation in mouse models (PMID: 16187797).
V802I missense unknown EGFR V802I lies within the protein kinase domain of the Egfr protein (UniProt.org). V802I has been identified in sequencing studies (PMID: 24040454), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
L747_A750del deletion gain of function - predicted EGFR L747_A750del results in the deletion of four amino acids in the protein kinase domain of the Egfr protein from amino acids 747 to 750 (UniProt.org). L747_A750del has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other EGFR exon 19 deletion mutations (PMID: 19147750).
L798H missense unknown EGFR L798H lies within the protein kinase domain of the Egfr protein (UniProt.org). L798H has been identified in the scientific literature (PMID: 16870303), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
N826S missense unknown EGFR N826S lies within the protein kinase domain of the Egfr protein (UniProt.org). N826S results in constitutive Egfr phosphorylation, activation of downstream Erk, Stat5, and Akt signaling, transformation of cultured cells, and is associated with drug resistance in one study (PMID: 19147750), however, in another study N826S demonstrates transforming activity similar to wild-type Egfr in two different cell lines (PMID: 29533785), and therefore, its effect on Egfr protein function is unknown. Y
T751I missense unknown EGFR T751I lies within the protein kinase domain of the Egfr protein (UniProt.org). T751I is predicted to be an activating, oncogenic mutation based on SIFT analysis (PMID: 18006781), but has not been biochemically characterized and therefore its effect on Egfr protein function is unknown (PubMed, Mar 2019).
G719C missense gain of function EGFR G719C lies within the phosphate-binding P-loop in the protein kinase domain of the Egfr protein (PMID: 17349580). G719C confers a gain of function to Egfr, as indicated by constitutive autophosphorylation in cell culture (PMID: 19671738) and the ability to induce cell proliferation and cell viability in culture (PMID: 29533785).
M766_A767insAA insertion gain of function - predicted EGFR M766_A767insAA results in the insertion of two amino acids in the protein kinase domain of the Egfr protein between amino acids 766 and 767 (UniProt.org). M766_A767insAA results in growth factor-independent proliferation of cells in culture in one study (PMID: 29467275) and therefore, is predicted to lead to a gain of Egfr protein function.
A750P missense unknown EGFR A750P lies within the protein kinase domain of the Egfr protein (UniProt.org). A750P results in ligand-independent phosphorylation of Egfr in cell culture and promotes tumor formation in xenograft models in one study (PMID: 19625781), but induces similar cell proliferation and cell viability as wild-type Egfr in two different cell lines in another study (PMID: 29533785), and therefore, its effect on Egfr protein function is unknown.
V292M missense unknown EGFR V292M lies within the extracellular domain of the Egfr protein (UniProt.org). V292M demonstrates increased cell proliferation and cell viability as compared to wild-type Egfr in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown.
L833* nonsense unknown EGFR L833* results in a premature truncation in the protein kinase domain of the Egfr protein at amino acid 833 of 1210 (UniProt.org). L833* demonstrates greater than 24.5-fold growth advantage in IL-3-depeleted cells in culture, as compared to wild-type Egfr (PMID: 30952700), but the assay has not been validated and therefore, the functional effect of L833* on Egfr protein function is unknown.
EGFR - PURB fusion unknown EGFR-PURB results from the fusion of EGFR and PURB (PMID: 27102076). EGFR-PURB has been identified in lung adenocarcinoma (PMID: 27102076), but has not been biochemically characterized and therefore, the effect on fusion protein function is unknown (PubMed, Feb 2019).
R108K missense gain of function EGFR R108K lies within the extracellular domain of the Egfr protein (PMID: 17177598). R108K confers a gain of function on Egfr, as indicated by increased autophosphorylation, is transforming in cell culture, and promotes tumor formation in mouse models (PMID: 17177598).
K754H missense unknown EGFR K754H lies within the protein kinase domain of the Egfr protein (UniProt.org). K754H has not been characterized in the scientific literature and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
L718Q missense no effect - predicted EGFR L718Q lies within the protein kinase domain of the Egfr protein (UniProt.org). L718Q is predicted to have no effect on Egfr protein function as indicated by a lack of transforming ability in culture in one study, and is associated with resistance to third-generation Egfr inhibitors (PMID: 25948633). Y
Q432R missense unknown EGFR Q432R lies within the approximate repeat of the Egfr protein (UniProt.org). Q432R has not been characterized in the scientific literature and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
K737E missense no effect - predicted EGFR K737E lies within the cytoplasmic domain of the Egfr protein (UniProt.org). K737E results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
G810D missense unknown EGFR G810D lies within the protein kinase domain of the Egfr protein (UniProt.org). G810D has been identified in the scientific literature (PMID: 17224267, PMID: 26462025, PMID: 26901614), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
R831H missense gain of function - predicted EGFR R831H lies within the protein kinase domain of the Egfr protein (UniProt.org). R831H results in increased Egfr phosphorylation in cell culture in one study (PMID: 20942962) and therefore, is predicted to lead to a gain of Egfr protein function.
T751_I759delinsN indel gain of function - predicted EGFR T751_I759delinsN results in a deletion of nine amino acids in the protein kinase domain of the Egfr protein from aa 751 to aa 759, combined with the insertion of an asparagine (N) at the same site (UniProt.org). T751_I759delinsN has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other EGFR exon 19 deletion and deletion-insertion mutations (PMID: 19147750, PMID: 22190593, PMID: 23387505).
A750V missense unknown EGFR A750V lies within the protein kinase domain of the Egfr protein (UniProt.org). A750V has been demonstrated to confer resistance to Egfr inhibitors as a secondary resistance mutation (PMID: 18588508), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019). Y
K467T missense gain of function EGFR K467T lies within the extracellular domain of the Egfr protein (UniProt.org). K467T results in increased Egfr and Erk phosphorylation and confers resistance to Erbitux (cetuximab) in cell culture (PMID: 26843189). Y
S768N missense no effect EGFR S768N lies within the protein kinase domain of the Egfr protein (UniProt.org). S768N does not result in increased Egfr phosphorylation or activation of Akt in cell culture (PMID: 21132006) and induces cell viability and proliferation similar to wild-type Egfr (PMID: 29533785).
G312W missense unknown EGFR G312W lies within the extracellular domain of the Egfr protein (UniProt.org). G312W results in increased transformation ability in one of two different cell lines in one study (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
R1052K missense unknown EGFR R1052K lies within the cytoplasmic domain of the Egfr protein (UniProt.org). R1052K demonstrates greater than 24.5-fold growth advantage in IL-3-depeleted cells in culture, as compared to wild-type Egfr (PMID: 30952700), but the assay has not been validated and therefore, the functional effect of R1052K on Egfr protein function is unknown.
M137K missense unknown EGFR M137K lies within the extracellular domain of the Egfr protein (UniProt.org). M137K demonstrates greater than 24.5-fold growth advantage in IL-3-depeleted cells in culture, as compared to wild-type Egfr (PMID: 30952700), but the assay has not been validated and therefore, the functional effect of M137K on Egfr protein function is unknown.
A289V missense gain of function EGFR A289V lies within the extracellular domain of the Egfr protein (PMID: 17177598). A289V confers a gain of function on Egfr, as indicated by increased ligand-independent Egfr phosphorylation and is transforming in cell culture (PMID: 17177598, PMID: 29533785).
H773dup duplication gain of function EGFR H773dup (also referred to as H773_V774insH) indicates the insertion of the duplicate amino acid, histidine (H)-773, in the protein kinase domain of the Egfr protein (UniProt.org). H773dup results in constitutive phosphorylation of Egfr and activation of downstream signaling in cell culture (PMID: 24353160).
K467X missense unknown EGFR K467X indicates any Egfr missense mutation which results in the lysine (K) at amino acid 467 being replaced by a different amino acid.
V1133M missense unknown EGFR V1133M lies within the cytoplasmic domain of the Egfr protein (UniProt.org). V1133M demonstrates greater than 24.5-fold growth advantage in IL-3-depeleted cells in culture, as compared to wild-type Egfr (PMID: 30952700), but the assay has not been validated and therefore, the functional effect of V1133M on Egfr protein function is unknown.
E709X missense unknown EGFR E709X indicates any Egfr missense mutation which results in the glutamic acid (E) at amino acid 709 being replaced by a different amino acid. EGFR E709 mutations are considered "hotspot" mutations (PMID: 18372921).
L838M missense no effect - predicted EGFR L838M lies within the protein kinase domain of the Egfr protein (UniProt.org). L838M results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
V769_D770insGVV insertion gain of function - predicted EGFR V769_D770insGVV results in the insertion of three amino acids in the protein kinase domain of the Egfr protein between amino acids 769 and 770 (UniProt.org). V769_D770insGVV has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other Egfr exon 20 insertions (PMID: 24353160).
L861Q missense gain of function EGFR L861Q lies within the protein kinase domain of the Egfr protein (UniProt.org). L861Q confers a gain of function to Egfr, as indicated by increased Egfr kinase activity in cell culture (PMID: 23387505, PMID: 21252719).
I475V missense no effect - predicted EGFR I475V lies within the extracellular domain of the Egfr protein (UniProt.org). I475V results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
P596S missense gain of function - predicted EGFR P596S lies within the extracellular domain of the Egfr protein (UniProt.org). P596S results in increased transformation ability in two different cell lines in one study (PMID: 29533785) and therefore, is predicted to lead to a gain of Egfr protein function.
mutant unknown unknown EGFR mut indicates an unspecified mutation in the EGFR gene.
V851A missense loss of function EGFR V851A lies within the protein kinase domain of the Egfr protein (UniProt.org). V851A results in a loss of Egfr kinase activity, reduced activity of the activating EGFRvIII variant in the context of complex mutations, and is not transforming in cell culture (PMID: 19147750).
E513D missense no effect - predicted EGFR E513D lies within the extracellular domain of the Egfr protein (UniProt.org). E513D results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
E709H missense unknown EGFR E709H lies within the cytoplasmic domain of the Egfr protein (UniProt.org). E709H has been identified in the scientific literature (PMID: 17409929, PMID: 15604253), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
P794S missense no effect - predicted EGFR P794S lies within the cytoplasmic domain of the Egfr protein (UniProt.org). P794S results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
R252C missense no effect - predicted EGFR R252C lies within the extracellular domain of the Egfr protein (UniProt.org). R252C results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
S720C missense unknown EGFR S720C lies within the protein kinase domain of the Egfr protein (UniProt.org). S720C has been identified in the scientific literature (PMID: 28196074), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
H773_V774dup duplication gain of function - predicted EGFR H773_V774dup indicates the insertion of 2 duplicate amino acids, histidine (H)-773 through valine (V)-774, in the protein kinase domain of the Egfr protein (UniProt.org). H773_V774dup has not been biochemically characterized, but is predicted to lead to Egfr activation based on the effect of other Egfr exon 20 insertions (PMID: 24353160, PMID: 16187797).
T402S missense unknown EGFR T402S lies within the extracellular domain of the Egfr protein (UniProt.org). T402S demonstrates greater than 24.5-fold growth advantage in IL-3-depeleted cells in culture, as compared to wild-type Egfr (PMID: 30952700), but the assay has not been validated and therefore, the functional effect of T402S on Egfr protein function is unknown.
A1118T missense unknown EGFR A1118T lies within the cytoplasmic domain of the Egfr protein (UniProt.org). A1118T has been identified in the scientific literature (PMID: 29141884), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
L833V missense gain of function - predicted EGFR L833V lies within the protein kinase domain of the Egfr protein (UniProt.org). L833V results in increased transformation ability in two different cell lines in one study (PMID: 29533785) and therefore, is predicted to lead to a gain of Egfr protein function.
I213M missense unknown EGFR I213M lies within the extracellular domain of the Egfr protein (UniProt.org). I213M has been identified in sequencing studies (J Clin Oncol 37, 2019 (suppl; abstr e13000)), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Jun 2019).
R776S missense unknown EGFR R776S lies within the protein kinase domain of the Egfr protein (UniProt.org). R776S has been identified in the scientific literature (PMID: 29769567), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
L858K missense unknown EGFR L858K lies within the protein kinase domain of the Egfr protein (UniProt.org). L858K has been identified in the scientific literature (PMID: 23754386), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
R1052I missense unknown EGFR R1052I lies within the cytoplasmic domain of the Egfr protein (UniProt.org). R1052I has been identified in the scientific literature (PMID: 28566434), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
D1009N missense no effect - predicted EGFR D1009N lies within the cytoplasmic domain of the Egfr protein (UniProt.org). D1009N results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
V765L missense unknown EGFR V765L lies within the protein kinase domain of the Egfr protein between (UniProt.org). V765L has been identified in the scientific literature (PMID: 28747773), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
R98Q missense no effect - predicted EGFR R98Q lies within the extracellular domain of the Egfr protein (UniProt.org). R98Q results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
P733S missense unknown EGFR P733S lies within the protein kinase domain of the Egfr protein (UniProt.org). P733S has been identified in the scientific literature (PMID: 21949883, PMID: 16514409), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
Q787R missense gain of function - predicted EGFR Q787R lies within the cytoplasmic domain of the Egfr protein (UniProt.org). Q787R results in increased transformation ability in two different cell lines in one study (PMID: 29533785) and therefore, is predicted to lead to a gain of Egfr protein function.
D770_N771insSVD insertion gain of function - predicted EGFR D770_N771insSVD results in the insertion of three amino acids in the protein kinase domain of the Egfr protein between amino acids 770 and 771 (UniProt.org). D770_N771insSVD has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other Egfr exon 20 insertions (PMID: 24353160).
V765A missense unknown EGFR V765A lies within the protein kinase domain of the Egfr protein (UniProt.org). V765A has been identified in the scientific literature (PMID: 15897572, PMID: 19671843, PMID: 20346742), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
R889G missense unknown EGFR R889G lies within the protein kinase domain of the Egfr protein (UniProt.org). R889G has been identified in the sequencing studies (PMID: 25189529), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
E709G missense gain of function EGFR E709G lies within the cytoplasmic domain of the Egfr protein (UniProt.org). E709G confers a gain of function to Egfr, as indicated by constitutive Egfr phosphorylation in cell culture (PMID: 16205628) and the ability to induce cell proliferation and cell viability in culture (PMID: 29533785).
P373Q missense no effect - predicted EGFR P373Q lies within the extracellular domain of the Egfr protein (UniProt.org). P373Q results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
S784Y missense unknown EGFR S784Y lies within the protein kinase domain of the Egfr protein (UniProt.org). S784Y has been identified in the scientific literature (PMID: 17224267, PMID: 22317764), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
I1018N missense unknown EGFR I1018N lies within the cytoplasmic domain of the Egfr protein (UniProt.org). I1018N demonstrates greater than 24.5-fold growth advantage in IL-3-depeleted cells in culture, as compared to wild-type Egfr (PMID: 30952700), but the assay has not been validated and therefore, the functional effect of I1018N on Egfr protein function is unknown.
R803W missense unknown EGFR R803W lies within the protein kinase domain of the Egfr protein (UniProt.org). R803W has been identified in the scientific literature (PMID: 27086595), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
L838V missense gain of function EGFR L838V lies within the protein kinase domain of the Egfr protein (UniProt.org). L838V results in constitutive Egfr phosphorylation and activation of downstream ERK, Stat5, and AKT, and transformation of cultured cells (PMID: 19147750, PMID: 29533785).
L1087P missense no effect - predicted EGFR L1087P lies within the cytoplasmic domain of the Egfr protein (UniProt.org). L1087P results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
G735A missense unknown EGFR G735A lies within the protein kinase domain of the Egfr protein (UniProt.org). G735A has not been characterized in the scientific literature and therefore, its effect on Egfr protein function is unknown (PubMed, Nov 2018).
N771dup duplication gain of function - predicted EGFR N771dup (also referred to as D770_N771insN) indicates the insertion of the duplicate amino acid, asparagine (N)-771, in the protein kinase domain of the Egfr protein (UniProt.org). N771dup has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other Egfr exon 20 insertions (PMID: 16187797).
L747_A750delinsP indel gain of function - predicted EGFR L747_A750delinsP results in a deletion of four amino acids in the protein kinase domain of the Egfr protein from aa 746 to aa 750, combined with the insertion of a proline (P) at the same site (UniProt.org). L747_A750delinsP results in increased transformation ability in two different cell lines in one study (PMID: 29533785) and therefore, is predicted to lead to a gain of Egfr protein function.
E746_A750delinsIP indel gain of function - predicted EGFR E746_A750delinsIP results in a deletion of five amino acids in the protein kinase domain of the Egfr protein from aa 746 to aa 750, combined with the insertion of an isoleucine (I) and a proline (P) at the same site (UniProt.org). E746_A750delinsIP has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other EGFR exon 19 deletion and deletion-insertion mutations (PMID: 19147750, PMID: 22190593, PMID: 23387505).
EGFR - PPARGC1A fusion gain of function EGFR-PPARGC1A results from the fusion of EGFR and PPARGC1A, which leads to constitutive phosphorylation and activation of Egfr signaling, and tumor formation in animal models (PMID: 28978917). EGFR-PPARGC1A has been identified in cutaneous squamous cell carcinoma (PMID: 28978917).
L792H missense unknown EGFR L792H lies within the protein kinase domain in the Egfr protein (UniProt.org). L792H has been demonstrated to occur as a secondary drug resistance mutation (PMID: 28093244, PMID: 28625641), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019). Y
V769_D770insGSV insertion gain of function - predicted EGFR V769_D770insGSV results in the insertion of three amino acids in the protein kinase domain of the Egfr protein between amino acids 769 and 770 (UniProt.org). V769_D770insGSV has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other Egfr exon 20 insertions (PMID: 24353160).
G779S missense unknown EGFR G779S lies within the protein kinase domain of the Egfr protein (UniProt.org). G779S has been identified in the scientific literature (PMID: 17626639, PMID: 22528563), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
E45Q missense no effect - predicted EGFR E45Q lies within the extracellular domain of the Egfr protein (UniProt.org). E45Q results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
T363I missense gain of function - predicted EGFR T363I lies within the extracellular domain of the Egfr protein (UniProt.org). T363I results in increased transformation ability in two different cell lines in one study (PMID: 29533785) and therefore, is predicted to lead to a gain of Egfr protein function.
L90F missense unknown EGFR L90F lies within the extracellular domain of the Egfr protein (UniProt.org). L90F has been identified in sequencing studies (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
T725M missense gain of function EGFR T725M lies within the protein kinase domain of the Egfr protein (Uniprot.org). T725M results in increased Egfr autophosphorylation and downstream signaling in cell culture (PMID: 24743239).
S1153I missense unknown EGFR S1153I lies within the cytoplasmic domain of the Egfr protein (UniProt.org). S1153I has been identified in the scientific literature (PMID: 29141884), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
D770delinsGY indel gain of function EGFR D770delinsGY results in a deletion of aspartic acid (D) at amino acid 770 within the protein kinase domain of the Egfr protein, combined with the insertion of a glycine (G) and a tyrosine (Y) at the same site (UniProt.org). D770delinsGY results in autophosphorylation of Egfr, transformation of cultured cells, and is associated with resistance to some Egfr inhibitors (PMID: 28363995). Y
L688P missense loss of function EGFR L688P lies within the protein kinase domain of the Egfr protein (UniProt.org). L688P results in a loss of Egfr kinase activity, reduced activity of the activating EGFRvIII variant in the context of complex mutations, and is not transforming in cell culture (PMID: 19147750).
L792P missense unknown EGFR L792P lies within the protein kinase domain of the Egfr protein (UniProt.org). L792P has been identified in the scientific literature (PMID: 16014883, PMID: 27895798), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
R222C missense gain of function - predicted EGFR R222C lies within the extracellular domain of the Egfr protein (UniProt.org). R222C results in increased transformation ability in two different cell lines in one study (PMID: 29533785) and therefore, is predicted to lead to a gain of Egfr protein function.
A120P missense unknown EGFR A120P lies within the L1 domain of the Egfr protein (PMID: 19390622). A120P has been identified in the sequencing studies (PMID: 24983367), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
V769L missense gain of function - predicted EGFR V769L lies within the protein kinase domain of the Egfr protein (UniProt.org). V769L is predicted to lead to a gain of Egfr protein function as indicated by increased cell viability and proliferation in two cell lines in one study (PMID: 29533785), and is associated with resistance to Egfr tyrosine kinase inhibitors (PMID: 18588508). Y
G696E missense unknown EGFR G696E lies within the cytoplasmic domain of the Egfr protein (UniProt.org). G696E has been identified in the scientific literature (PMID: 28229982), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
K593Q missense unknown EGFR K593Q lies within the extracellular domain of the Egfr protein (UniProt.org). K593Q has been identified in sequencing studies (J Clin Oncol 37, 2019 (suppl; abstr e13000)), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Jun 2019).
R677H missense unknown EGFR R677H lies within the cytoplasmic domain of the Egfr protein (UniProt.org). R677H has been identified in sequencing studies (PMID: 28247034), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Apr 2019).
H988P missense unknown EGFR H988P lies within the cytoplasmic domain of the Egfr protein (UniProt.org). H988P is predicted to interfere with Egfr dimerization by computational modeling (PMID: 20049516), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Apr 2019).
G735S missense unknown EGFR G735S lies within the protein kinase domain of the Egfr protein (UniProt.org). G735S results in ligand-independent Egfr phosphorylation, activation of the Erk signaling pathway, and is transforming in cell culture (PMID: 18193092), however in another study, G735S induces similar cell proliferation and cell viability as wild-type Egfr in two different cell lines (PMID: 29533785), and therefore, its effect on Egfr protein function is unknown.
loss unknown loss of function EGFR loss indicates loss of the EGFR gene, mRNA, and protein.
N700D missense unknown EGFR N700D lies within the cytoplasmic domain of the Egfr protein (UniProt.org). N700D has been identified in the scientific literature (PMID: 20127001, PMID: 15897572), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
A698T missense unknown EGFR A698T lies within a region of the Egfr protein important for dimerization, phosphorylation, and activation (UniProt.org). A698T has been identified in the scientific literature (PMID: 20371674), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
EGFR - FGFR1 fusion unknown EGFR-FGFR1 results from the fusion of EGFR and FGFR1 (PMID: 29883838). EGFR-FGFR1 has been identified in non-small cell lung cancer (PMID: 29883838), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Apr 2019).
E868G missense unknown EGFR E868G lies within the protein kinase domain of the Egfr protein (UniProt.org). E868G results in increased Egfr activation in cell culture (PMID: 20942962), however, in another study, E868G induces similar cell proliferation and cell viability levels as wild-type Egfr in one of two different cell lines (PMID: 29533785), and therefore, its effect on Egfr protein function is unknown.
V843L missense unknown EGFR V843L lies within the protein kinase domain of the Egfr protein (UniProt.org). V843L results in decreased cell proliferation and cell viability as compared to wild-type Egfr in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown.
V148M missense unknown EGFR V148M lies within the extracellular domain of the Egfr protein (UniProt.org). V148M results in increased cell proliferation and cell viability as compared to wild-type Egfr in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown.
A702V missense gain of function - predicted EGFR A702V lies within a region of the Egfr protein important for dimerization, phosphorylation, and activation (UniProt.org). A702V is predicted to confer a gain of function to the Egfr protein, as demonstrated by greater than 24.5-fold growth advantage in IL-3-depeleted cells in culture, as compared to wild-type Egfr, and confirmed in additional assays (PMID: 30952700).
V592I missense no effect EGFR V592I lies within the extracellular domain of the Egfr protein (UniProt.org). V592I results in similar cell proliferation and viability levels as wild-type Egfr in culture (PMID: 29533785, PMID: 28979142) and similar levels of autophosphorylation (PMID: 28979142) and therefore, has no effect on Egfr protein function.
V765_M766delinsHH indel unknown EGFR V765_M766delinsHH results in a deletion of two amino acids in the protein kinase domain of the Egfr protein from aa 745 to aa 746, combined with the insertion of two histidines (H) at the same site (UniProt.org). V765_M766delinsHH has been demonstrated to confer resistance to some Egfr inhibitors in culture (PMID: 29467275), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019). Y
D256Y missense unknown EGFR D256Y lies within the extracellular domain of the Egfr protein (UniProt.org). D256Y demonstrates increased transformation ability compared to wild-type Egfr in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown.
V292L missense unknown EGFR V292L lies within the approximate repeat of the Egfr protein (UniProt.org). V292L has been identified in the scientific literature (PMID: 29141884), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
S768I missense gain of function EGFR S768I lies within the protein kinase domain of the Egfr protein (UniProt.org). S768I results in constitutive phosphorylation of Egfr, increased downstream signaling, and is transforming in cell culture (PMID: 19147750, PMID: 29533785).
I740_K745dup duplication gain of function - predicted EGFR I740_K745dup (also referred to as K745_E746insIPVAIK) indicates the insertion of 6 duplicate amino acids, idoleucine (I)-740 through lysine(K)-745, in the protein kinase domain of the Egfr protein (UniProt.org). I740_K745dup has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other EGFR exon 19 insertion mutations (PMID: 22190593).
T790M missense gain of function EGFR T790M is a gatekeeper mutation that lies within the ATP-binding pocket in the protein kinase domain of the Egfr protein (PMID: 20026433). T790M results in increased Egfr kinase activity, is transforming in culture (PMID: 30952700), and frequently occurrs as secondary somatic mutation that confers resistance to reversible tyrosine kinase inhibitors (PMID: 17671201, PMID: 18227510, PMID: 20026433). Y
E709Q missense unknown EGFR E709Q lies within the cytoplasmic domain of the Egfr protein (UniProt.org). E709Q results in increased cell proliferation and cell viability as compared to wild-type Egfr in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown.
V742A missense unknown EGFR V742A lies within the protein kinase domain of the Egfr protein (UniProt.org). V742A results in growth factor-independent cell proliferation in culture (PMID: 19147750), however, demonstrates increased cell proliferation and cell viability levels compared to wild-type Egfr in one cell type, but decreased levels in another cell type in culture (PMID: 29533785), and therefore, its effect on Egfr protein function is unknown.
L792_M793insHIV insertion gain of function - predicted EGFR L792_M793insHIV results in the insertion of three amino acids in the protein kinase domain of the Egfr protein between amino acids 792 and 793 (UniProt.org). L792_M793insHIV has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other Egfr exon 20 insertions (PMID: 24353160).
D368Y missense unknown EGFR D368Y lies within the extracellular domain of the Egfr protein (UniProt.org). D368Y has been identified in sequencing studies (J Clin Oncol 37, 2019 (suppl; abstr e13000)), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Jun 2019).
E868V missense unknown EGFR E868V lies within the protein kinase domain of the Egfr protein (UniProt.org). E868V has been identified in the scientific literature (PMID: 18379359), but not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
D770N missense unknown EGFR D770N lies within the protein kinase domain of the Egfr protein (UniProt.org). D770N has been identified in the scientific literature (PMID: 23371856), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
L858Q missense unknown EGFR L858Q lies within the protein kinase domain of the Egfr protein (UniProt.org). The functional effect of L858Q is conflicting, as it results in autophosphorylation to similar levels of wild-type Egfr, but leads to increased Akt activation in the presence of Egf compared to wild-type Egfr in cell culture (PMID: 24743239).
D770_N771insGL insertion gain of function - predicted EGFR D770_N771insGL results in the insertion of two amino acids in the protein kinase domain of the Egfr protein between amino acids 770 and 771 (UniProt.org). D770_N771insGL has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other Egfr exon 20 insertions (PMID: 24353160).
Q791R missense unknown EGFR Q791R lies with the protein kinase domain of the Egfr protein (UniProt.org). Q791R has been demonstrated to confer resistance to some third generation EGFR inhibitors (PMID: 25948633), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019). Y
I491M missense gain of function EGFR I491M lies within the extracellular domain of the Egfr protein (UniProt.org). I491M results in increased Egfr and Erk phosphorylation and confers resistance to Erbitux (cetuximab) and Vectibix (panitumumab) in cell culture (PMID: 26843189). Y
E746_S752delinsV indel gain of function - predicted EGFR E746_S752delinsV results in a deletion of seven amino acids in the protein kinase domain of the Egfr protein from aa 746 to aa 752, combined with the insertion of a valine (V) at the same location (UniProt.org). E746_S752delinsV has not been biochemically characterized, but is predicted to lead to a gain of Egfr function as indicated by increased cell proliferation and cell viability in two different cell lines in one study (PMID: 29533785).
A839V missense unknown EGFR A839V lies within the protein kinase domain of the Egfr protein (UniProt.org). A839V demonstrates decreased transformation ability as compared to wild-type Egfr in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Apr 2019).
E282K missense no effect - predicted EGFR E282K lies within the extracellular domain of the Egfr protein (UniProt.org). E282K results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
A864V missense unknown EGFR A864V lies within the protein kinase domain of the Egfr protein (UniProt.org). A864V has been identified in the scientific literature (PMID: 25343854, PMID: 18701186, PMID: 28223509), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
D770_N771insSVE insertion gain of function - predicted EGFR D770_N771insSVE results in the insertion of three amino acids in the protein kinase domain of the Egfr protein between amino acids 770 and 771 (UniProt.org). D770_N771insSVE has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other Egfr exon 20 insertions (PMID: 24353160).
del deletion loss of function EGFR del indicates a deletion of the EGFR gene.
D761_E762insEAFQ insertion gain of function - predicted EGFR D761_E762insEAFQ results in the insertion of four amino acids in the protein kinase domain of the Egfr protein between amino acids 761 and 762 (UniProt.org). D761_E762insEAFQ has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other Egfr exon 20 insertions (PMID: 24353160).
R841K missense unknown EGFR R841K lies within the protein kinase domain of the Egfr protein (UniProt.org). The functional effect of R841K is conflicting, as it demonstrates decreased Egfr phosphorylation comparable to wild-type Egfr and is not transforming (PMID: 27427230, PMID: 18193092), but also leads to moderate ligand dependent activation of Akt, ligand independent activation of Stat5 and Erk, and ligand dependent increase in proliferation in cell culture (PMID: 18193092).
K754E missense gain of function EGFR K754E lies within the protein kinase domain of the Egfr protein (UniProt.org). K754E results in increased Egfr phosphorylation in culture, promotes tumor formation in animal models (PMID: 27478040).
A859T missense unknown EGFR A859T lies within the protein kinase domain of the Egfr protein (UniProt.org). A859T results in lower autophosphorylation levels compared to activating mutation L858R in culture (PMID: 17877814), but demonstrates increased cell proliferation and cell viability as compared to wild-type Egfr in one of two different cell lines in culture (PMID: 29533785), and therefore, its effect on Egfr protein function is unknown.
H773L missense unknown EGFR H773L lies within the protein kinase domain of the Egfr protein (UniProt.org). H773L confers resistance to Egfr tyrosine kinase inhibitors in culture (PMID: 17974985), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Apr 2019). Y
L747_P753delinsS indel gain of function EGFR L747_P753delinsS results in a deletion of seven amino acids in the protein kinase domain of the Egfr protein from aa 747 to aa 753, combined with the insertion of a serine (S) at the same location (UniProt.org). L747_P753delinsS results in autophosphorylation of the Egfr protein and transformation of cultured cells (PMID: 19147750, PMID: 29533785).
A767_V769dup duplication gain of function EGFR A767_V769dup (also referred to as V769_D770insASV) indicates the insertion of 3 duplicate amino acids, alanine (A)-767 through valine (V)-769, in the protein kinase domain of the Egfr protein (UniProt.org). A767_V769dup results in constitutive Egfr phosphorylation, downstream signaling activation, and transformation of cultured cells (PMID: 24353160, PMID: 28363995).
P753S missense unknown EGFR P753S lies within the protein kinase domain of the Egfr protein (UniProt.org). P753S has been identified in the scientific literature (PMID: 24934779, PMID: 25960661), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
P1170H missense unknown EGFR P1170H lies within the cytoplasmic domain of the Egfr protein (UniProt.org). The functional effect of P1170H is conflicting, as P1170H demonstrated greater than 24.5-fold growth advantage in IL-3-depeleted cells in culture, as compared to wild-type Egfr (PMID: 30952700), but in another assay in the same study, P1170H did not induce cell proliferation in the absence of IL-3 (PMID: 30952700).
E561K missense unknown EGFR E561K lies within the extracellular domain of the Egfr protein (UniProt.org). E561K demonstrates greater than 24.5-fold growth advantage in IL-3-depeleted cells in culture, as compared to wild-type Egfr (PMID: 30952700), but the assay has not been validated and therefore, the functional effect of E561K on Egfr protein function is unknown.
L692P missense unknown EGFR L692P lies within a region important for dimerization, phosphorylation, and activation of the Egfr protein (UniProt.org). L692P has been identified in the scientific literature (PMID: 19238633, PMID: 18000506), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
P596L missense gain of function - predicted EGFR P596L lies within the extracellular domain of the Egfr protein (UniProt.org). P596L results in increased transformation ability in two different cell lines in one study (PMID: 29533785) and therefore, is predicted to lead to a gain of Egfr protein function.
A743T missense unknown EGFR A743T lies within the protein kinase domain of the Egfr protein (UniProt.org). A743T has been identified in the scientific literature (PMID: 18258923, PMID: 24891042), but not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
V769_D770insASV insertion gain of function - predicted EGFR V769_D770insASV results in the insertion of three amino acids in the protein kinase domain of the Egfr protein between amino acids 769 and 770 (UniProt.org). V769_D770insASV has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other Egfr exon 20 insertions (PMID: 24353160).
K745M missense loss of function EGFR K745M (also referred to as K721M in the post-translationally processed Egfr protein) lies within the protein kinase domain of the Egfr protein (PMID: 20495563, UniProt.org). K745M results in a loss of Egfr kinase activity in cultured cells (PMID: 3498122, PMID: 19560417, PMID: 21081186).
N444S missense unknown EGFR N444S lies within the extracellular domain of the Egfr protein (UniProt.org). N444S results in increased cell proliferation and cell viability as compared to wild-type Egfr in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown.
K745_E749del deletion gain of function - predicted EGFR K745_E749del results in the deletion of five amino acids in the protein kinase domain of the Egfr protein from amino acids 745 to 749 (UniProt.org). K745_E749del has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other EGFR exon 19 deletion mutations (PMID: 16373402, PMID: 16912195, PMID: 23387505).
G719X missense unknown G719X indicates a single amino acid change in the phosphate-binding “P loop” of the kinase domain of the Egfr protein (PMID: 17349580). G719X is predicted to lead to a gain of function as the substitution (usually A, C, or S) likely destabilizes the P loop, weakening the inactive conformation of Egfr (PMID: 17349580).
T263P missense gain of function EGFR T263P lies within the extracellular domain of the Egfr protein (PMID: 17177598). T263P leads to increased Egfr phosphorylation (PMID: 17177598), transformation of cultured cells (PMID: 29533785), and results in increased tumor growth in mouse models (PMID: 17177598).
H773Y missense unknown EGFR H773Y lies within the protein kinase domain of the Egfr protein (UniProt.org). H773Y has been identified in the scientific literature (PMID: 15753462, PMID: 19536777, PMID: 23139256), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
S784F missense unknown EGFR S784F lies within the protein kinase domain of the Egfr protein (UniProt.org). S784F results in constitutive Egfr phosphorylation, activation of downstream signaling, and is transforming in culture (PMID: 19147750), however, in another study, S784F induces cell proliferation and cell viability similar to wild-type Egfr in culture (PMID: 29533785), and therefore, its effect on Egfr protein function is unknown.
over exp none no effect EGFR over exp indicates an over expression of the Egfr protein and/or mRNA. However, the mechanism causing the over expression is unspecified.
V689M missense gain of function EGFR V689M (also referred to as V665M) lies within the juxtamembrane domain of the Egfr protein (PMID: 21165163). V698M results in constitutive activation of Egfr and is transforming in cell culture, and leads to increased tumor growth in mouse models (PMID: 19560417, PMID: 21165163).
A871T missense no effect - predicted EGFR A871T lies within the protein kinase domain of the Egfr protein (UniProt.org). A871T is predicted to have no effect on Egfr protein function as indicated by similar cell proliferation and viability levels as wild-type Egfr in one study (PMID: 29533785), and confers resistance to Egfr inhibitors in culture (PMID: 29141884). Y
F712L missense no effect - predicted EGFR F712L lies within the protein kinase domain of the Egfr protein (UniProt.org). F712L results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
G465E missense gain of function EGFR G465E lies within the extracellular domain of the Egfr protein (UniProt.org). G465E results in increased Egfr and Erk phosphorylation and confers resistance to Erbitux (cetuximab) and Vectibix (panitumumab) in cell culture (PMID: 26416732). Y
H47Y missense unknown EGFR H47Y lies within the extracellular domain of the Egfr protein (UniProt.org). H47Y results in decreased cell proliferation and cell viability as compared to wild-type Egfr in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown.
P772R missense gain of function - predicted EGFR P772R lies within the cytoplasmic domain of the Egfr protein (UniProt.org). P772R results in increased transformation ability in two different cell lines in one study (PMID: 29533785) and therefore, is predicted to lead to a gain of Egfr protein function.
T751_E758del deletion gain of function - predicted EGFR T751_E758del results in the deletion of eight amino acids in the protein kinase domain of the Egfr protein from amino acids 751 to 758. T751_I758del has not been biochemically characterized, but is predicted to lead to a gain of function based on the effects of other Egfr exon 19 deletion mutations (PMID: 16373402, PMID: 23387505).
F795L missense unknown EGFR F795L lies within the protein kinase domain of the Egfr protein (UniProt.org). F795L has been identified in the scientific literature (PMID: 29434916), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
A763V missense unknown EGFR A763V lies within the protein kinase domain of the Egfr protein (UniProt.org). A763V has been identified in sequencing studies (PMID: 25589618), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Apr 2019). Y
S752F missense unknown EGFR S752F lies within the protein kinase domain of the Egfr protein (UniProt.org). S752F has been identified in the scientific literature (PMID: 27528220, PMID: 28951454), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
S784P missense unknown EGFR S784P lies within the protein kinase domain of the Egfr protein (UniProt.org). S784P has been identified in sequencing studies (PMID: 22483783, PMID: 29434916), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
S645C missense gain of function EGFR S645C lies within the extracellular domain of the Egfr protein (UniProt.org). S645C results in increased Egfr phosphorylation in culture, promotes tumor formation in animal models, and confers resistance to erlotinib in culture (PMID: 27478040). Y
S752P missense unknown EGFR S752P lies within the protein kinase domain of the Egfr protein (UniProt.org). S752P has been identified in the scientific literature (PMID: 20371674, PMID: 24389433), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
H773R missense unknown EGFR H773R lies within the protein kinase domain of the Egfr protein (UniProt.org). H773R has been identified in the scientific literature (PMID: 23584298, PMID: 15623594), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
S720P missense unknown EGFR S720P lies within the protein kinase domain of the Egfr protein (UniProt.org). S720P has been identified in the scientific literature (PMID: 26773740, PMID: 23468551, PMID: 30055651), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
K745_A750del deletion gain of function - predicted EGFR K745_A750del results in the deletion of six amino acids in the protein kinase domain of the Egfr protein from amino acids 745 to 750 (UniProt.org). K745_A750del has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other EGFR exon 19 deletion mutations (PMID: 16373402, PMID: 16912195, PMID: 23387505).
H773_V774insQ insertion gain of function - predicted EGFR H773_V774insQ results in the insertion of one amino acid in the protein kinase domain of the Egfr protein between amino acids 773 and 774 (UniProt.org). H773_V774insQ has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other EGFR exon 20 insertion mutations (PMID: 24353160).
G810A missense unknown EGFR G810A lies within the protein kinase domain of the Egfr protein (UniProt.org). G810A has not been characterized in the scientific literature and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
P272L missense loss of function - predicted EGFR P272L lies within the extracellular domain of the Egfr protein (UniProt.org). P272L results in decreased transformation ability as compared to wild-type Egfr in two different cell lines in one study (PMID: 29533785) and therefore, is predicted to lead to a loss of Egfr protein function.
Q1164R missense no effect - predicted EGFR Q1164R lies within the cytoplasmic domain of the Egfr protein (UniProt.org). Q1164R results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
D770_N771insGT insertion gain of function - predicted EGFR D770_N771insGT results in the insertion of two amino acids in the protein kinase domain of the Egfr protein between amino acids 770 and 771 (UniProt.org). D770_N771insGT has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other Egfr exon 20 insertions (PMID: 24353160).
F712Y missense unknown EGFR F712Y lies within the protein kinase domain of the Egfr protein (UniProt.org). F712Y has not been characterized in the scientific literature and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
I853T missense loss of function EGFR I853T lies within the protein kinase domain of the Egfr protein (UniProt.org). I853T results in a loss of Egfr kinase activity, reduced activity of the activating EGFRvIII variant in the context of complex mutations, and is not transforming in cell culture (PMID: 19147750).
L861R missense gain of function EGFR L861R lies within the protein kinase domain of the Egfr protein (UniProt.org). L861R results in increased Egfr autophosphorylation and downstream signaling in cell culture (PMID: 24743239) and induces cell proliferation and cell viability in culture (PMID: 29533785).
L833F missense unknown EGFR L833F lies within the protein kinase domain of the Egfr protein (UniProt.org). L833F has been identified in the scientific literature (PMID: 26762747, PMID: 25130612), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
T354M missense unknown EGFR T354M lies within the extracellular domain of the Egfr protein (UniProt.org). T354M results in decreased cell proliferation and cell viability as compared to wild-type Egfr in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown.
Q105H missense unknown EGFR Q105H lies within the extracellular domain of the Egfr protein (UniProt.org). The functional effect of Q105H is conflicting, as Q105H results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and in another has greater than 24.5-fold growth advantage in IL-3-depeleted cells in culture, as compared to wild-type Egfr (PMID: 30952700).
L703P missense unknown EGFR L703P lies within the region of the Egfr protein that is important for dimerization, phosphorylation and activation (UniProt.org). L703P has been identified in the scientific literature (PMID: 21057220), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
L858M missense unknown EGFR L858M lies within the protein kinase domain of the Egfr protein (UniProt.org). L858M demonstrates greater than 24.5-fold growth advantage in IL-3-depeleted cells in culture, as compared to wild-type Egfr (PMID: 30952700), but the assay has not been validated and therefore, the functional effect of L858M on Egfr protein function is unknown.
L747_P753delinsQ indel gain of function - predicted EGFR L747_P753delinsQ results in a deletion of seven amino acids in the protein kinase domain of the Egfr protein from aa 747 to aa 753, combined with the insertion of glutamine (Q) at the same site (UniProt.org). L747_P753delinsQ has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other EGFR exon 19 deletion and deletion-insertion mutations (PMID: 19147750, PMID: 22190593, PMID: 23387505).
P741L missense unknown EGFR P741L lies within the protein kinase domain of the Egfr protein (UniProt.org). P741L has been identified in the scientific literature (PMID: 21771097), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
V843I missense gain of function EGFR V843I lies within the protein kinase domain of the Egfr protein (UniProt.org). V843I leads to increased Egfr phosphorylation, activation of Stat5 and Erk in the presence of Egf, is associated with drug resistance (PMID: 25057940), and is transforming in cell culture (PMID: 29533785). Y
V765M missense unknown EGFR V765M lies within the protein kinase domain of the Egfr protein (UniProt.org). V765M has been identified in the scientific literature (PMID: 25343854, PMID: 21070477), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
D1072E missense no effect - predicted EGFR D1072E lies within the cytoplasmic domain of the Egfr protein (UniProt.org). D1072E results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
N604I missense unknown EGFR N604I lies within the extracellular domain of the Egfr protein (UniProt.org). The functional effect of N604I is conflicting, as N604I demonstrated greater than 24.5-fold growth advantage in IL-3-depeleted cells in culture, as compared to wild-type Egfr (PMID: 30952700), but in another assay in the same study, N604I did not induce cell proliferation in the absence of IL-3 (PMID: 30952700).
H835L missense unknown EGFR H835L lies within the protein kinase domain of the Egfr protein (UniProt.org). H835L results in increased cell proliferation and cell viability as compared to wild-type Egfr in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown.
T783A missense unknown EGFR T783A lies within the protein kinase domain of the Egfr protein (UniProt.org). T783A has been identified in the scientific literature (PMID: 15897572), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
S720F missense unknown EGFR S720F lies within the protein kinase domain of the Egfr protein (UniProt.org). S720F has been identified in the scientific literature (PMID: 23768755), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
D770_N771insMATP insertion gain of function - predicted EGFR D770_N771insMATP results in the insertion of four amino acids in the protein kinase domain of the Egfr protein between amino acids 770 and 771 (UniProt.org). D770_N771insMATP has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other Egfr exon 20 insertions (PMID: 24353160).
S306L missense unknown EGFR S306L lies within the extracellular domain of the Egfr protein (UniProt.org). S306L has been demonstrated to confer resistance to some EGFR inhibitors (PMID: 29141884), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019). Y
E746_S752del deletion gain of function - predicted EGFR E746_S752del results in the deletion of seven amino acids in the protein kinase domain of the Egfr protein from amino acids 746 to 752 (UniProt.org). E746_S752del has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other EGFR exon 19 deletion mutations (PMID: 16373402, PMID: 16912195, PMID: 23387505).
P699L missense loss of function - predicted EGFR P699L lies within a region of the Egfr protein that is important for dimerization, phosphorylation, and activation (UniProt.org). P699L is predicted to confer a loss of function on the Egfr protein as demonstrated by decreased transformation ability as compared to wild-type Egfr in two different cell lines in one study (PMID: 29533785), and is associated with resistance to Egfr inhibitors (PMID: 22722798). Y
R675Q missense unknown EGFR R675Q lies within the cytoplasmic domain of the Egfr protein (UniProt.org). R675Q has been identified in the scientific literature (PMID: 16278407, PMID: 28573640), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
E746_T751delinsVA indel gain of function - predicted EGFR E746_T751delinsVA results in a deletion of six amino acids in the protein kinase domain of the Egfr protein from amino acids 746 to 751, combined with the insertion of a valine (V) and an alanine (A) at the same site (UniProt.org). E746_T751delinsVA has not been biochemically characterized, but is predicted to lead to a gain of function based on the effect of other EGFR exon 19 deletion and deletion-insertion mutations (PMID: 19147750, PMID: 23387505).
V834L missense unknown EGFR V834L lies within the protein kinase domain of the Egfr protein (UniProt.org). V834L has been identified in the scientific literature (PMID: 29141884), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
L747_T751delinsP indel gain of function - predicted EGFR L747_T751delinsP results in the deletion of five amino acids in the protein kinase domain of the Egfr protein from amino acids 747 to 751, combined with the insertion of a proline (P) at the same site (UniProt.org). L747_T751delinsP has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other EGFR exon 19 deletion and deletion-insertion mutations (PMID: 19147750, PMID: 22190593, PMID: 23387505).
P699S missense unknown EGFR P699S lies within the cytoplasmic domain and a region of the Egfr protein that is important for dimerization, phosphorylation, and activation (UniProt.org). P699S results in decreased cell proliferation and cell viability as compared to wild-type Egfr in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown.
D761N missense gain of function EGFR D761N lies within the protein kinase domain of the Egfr protein (PMID: 19147750). D761N confers a gain of function to Egfr, as indicated by ligand-independent autophosphorylation, increased activation of downstream targets, and is transforming in cell culture (PMID: 19147750, PMID: 29533785).
G873E missense unknown EGFR G873E lies within the protein kinase domain of the Egfr protein (UniProt.org). G873E has been demonstrated to confer resistance to some EGFR inhibitors (PMID: 30404555), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
S220P missense no effect - predicted EGFR S220P lies within the extracellular domain of the Egfr protein (UniProt.org). S220P results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
K745R missense loss of function - predicted EGFR K745R lies within the protein kinase domain of the Egfr protein (UniProt.org). K745R results in a loss of Egfr phosphorylation in culture in one study (PMID: 17927978) and therefore, is predicted to lead to a loss of Egfr protein function.
Y764_V765insHH insertion gain of function - predicted EGFR Y764_V765insHH is an exon 20 mutation that results in the insertion 2 histidines (H) in the protein kinase domain of the Egfr protein between amino acids 764 and 765 (UniProt.org). Y764_V765insHH is predicted to lead to a gain of Egfr protein function as indicated by increased cell proliferation and cell viability in one study (PMID: 29533785), and is associated with resistance to Egfr inhibitors in culture (PMID: 29467275). Y
T710del deletion unknown EGFR T710del results in the deletion of an amino acid in the protein kinase domain of the Egfr protein at amino acid 710 (UniProt.org). T710del has been identified in the scientific literature (PMID: 17094398), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
wild-type none no effect Wild-type EGFR indicates that no mutation has been detected within the EGFR gene.
R776H missense gain of function EGFR R776H lies within the protein kinase domain of the Egfr protein (UniProt.org). R776H results in constitutive phosphorylation of Egfr, activation of Erk and Stat5 in cell culture (PMID: 23358982) and induces cell proliferation and cell viability in culture (PMID: 29533785).
D587H missense gain of function - predicted EGFR D587H lies within the extracellular domain of the Egfr protein (UniProt.org). D587H results in increased Egfr autophosphorylation in cell culture in one study (PMID: 27245685) and therefore, is predicted to lead to a gain of Egfr function.
M766_A767insAI insertion gain of function - predicted EGFR M766_A767insAI results in the insertion of two amino acids in the protein kinase domain of the Egfr protein between amino acids 766 and 767 (UniProt.org). M766_A767insAI results in increased transformation ability in two different cell lines in one study (PMID: 29533785) and therefore, is predicted to lead to a gain of Egfr protein function.
S498I missense unknown EGFR S498I lies within the extracellular domain of the Egfr protein (UniProt.org). S498I demonstrates greater than 24.5-fold growth advantage in IL-3-depeleted cells in culture, as compared to wild-type Egfr (PMID: 30952700), but the assay has not been validated and therefore, the functional effect of S498I on Egfr protein function is unknown.
G598V missense gain of function EGFR G598V lies within the extracellular domain of the Egfr protein (UniProt.org). G598V results in increased Egfr activity (PMID: 17177598), is transforming in cell culture (PMID: 29533785), and promotes tumor formation in mice (PMID: 17177598).
L703I missense unknown EGFR L703I lies within the cytoplasmic domain of the Egfr protein (UniProt.org). L703I has been demonstrated to confer resistance to some Egfr inhibitors (PMID: 29141884), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019). Y
W731* nonsense loss of function - predicted EGFR W731* results in a premature truncation in the protein kinase domain of the Egfr protein at amino acid 731 of 1210 (UniProt.org). Due to a loss of the protein kinase domain (UniProt.org, PMID: 15623594), W731* is predicted to lead to a loss of Egfr protein function.
G721C missense unknown EGFR G721C lies within the protein kinase domain of the Egfr protein (UniProt.org). G721C has been identified in the scientific literature (PMID: 27875527), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
T363N missense no effect - predicted EGFR T363N lies within the extracellular domain of the Egfr protein (UniProt.org). T363N results in similar cell proliferation and autophosphorylation as wild-type Egfr in culture (PMID: 28979142) and therefore, is predicted to have no effect on Egfr protein function.
G779F missense unknown EGFR G779F lies within the protein kinase domain of the Egfr protein (UniProt.org). G779F has been identified in the scientific literature (PMID: 16467085), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
R521K missense unknown EGFR R521K (also reported as R497K) lies within the repeat region of the Egfr protein (UniProt.org). R521K results in decreased growth in response to growth factors (PMID: 7937865), and in one of two cell lines, R521K demonstrates decreased cell proliferation and cell viability as compared to wild-type Egfr in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown.
S768_D770dup duplication gain of function - predicted EGFR S768_D770dup (also referred to as D770_N771insSVD) indicates the insertion of 3 duplicate amino acids, serine (S)-768 through aspartate (D)-770, in the protein kinase domain of the Egfr protein (UniProt.org). S768_D770dup results in increased Egfr phosphorylation and activation of downstream signaling in cell culture (PMID: 24353160), and results in IL-3-independent growth in culture PMID: 29686424).
L747S missense gain of function - predicted EGFR L747S lies within the protein kinase domain of the Egfr protein (UniProt.org). L747S is predicted to lead to a gain of function as indicated by increased transformation ability compared to wild-type Egfr in two different cell lines in one study (PMID: 29533785), and is associated with resistance to Egfr tyrosine kinase inhibitors (PMID: 24396447). Y
K745_E746insVPVAIK insertion gain of function - predicted EGFR K745_E746insVPVAIK results in the insertion of six amino acids in the protein kinase domain of the Egfr protein between amino acids 745 and 746 (UniProt.org). K745_E746insVPVAIK has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other EGFR exon 19 insertion mutations (PMID: 22190593).
G719A missense gain of function EGFR G719A lies within the P-loop in the kinase domain of the Egfr protein (PMID: 17349580). G719A results in increased cell proliferation and is transforming in cell culture (PMID: 26206867, PMID: 29533785).
P772_H773insPHA insertion gain of function - predicted EGFR P772_H773insPHA results in the insertion of three amino acids in the protein kinase domain of the Egfr protein between amino acids 772 and 773 (UniProt.org). P772_H773insPHA has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other Egfr exon 20 insertions (PMID: 24353160).
A755G missense unknown EGFR A755G lies within the protein kinase domain of the Egfr protein (UniProt.org). A755G has been identified in the scientific literature (PMID: 25304185), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
E746_E749del deletion gain of function - predicted EGFR E746_E749del results in the deletion of four amino acids in the protein kinase domain of the Egfr protein from amino acids 746 to 749 (UniProt.org). E746_E749del has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other EGFR exon 19 deletion mutations (PMID: 16373402, PMID: 16912195, PMID: 23387505).
F254I missense unknown EGFR F254I lies within the extracellular domain of the Egfr protein (UniProt.org). F254I has been identified in the scientific literature (PMID: 25910966), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
F856_G857insYIV insertion unknown EGFR F856_G857insYIV results in the insertion of three amino acids in the protein kinase domain of the Egfr protein between amino acids 856 and 857 (UniProt.org). F856_G857insYIV has not been characterized in the scientific literature and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
EGFR - SEPTIN14 fusion gain of function EGFR-SEPTIN14 results from the fusion of EGFR and SEPTIN14, demonstrating increased cell proliferation, self-renewal, migration, and activated STAT3 signaling in cell culture (PMID: 23917401). EGFR-SEPTIN14 has been identified in glioblastoma (PMID: 26762204, PMID: 23917401).
A702T missense unknown EGFR A702T lies within a region of the Egfr protein important for dimerization, phosphorylation, and activation (UniProt.org). A702T has been identified in the scientific literature (PMID: 19648884), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
I740_P741insIHR insertion gain of function - predicted EGFR I740_P741insIHR results in the insertion of three amino acids in the protein kinase domain of the Egfr protein between amino acids 740 and 741 (UniProt.org). I740_P741insIHR has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other EGFR exon 19 insertion mutations (PMID: 22190593).
N771_P772insRH insertion gain of function - predicted EGFR N771_P772insRH results in the insertion of two amino acids in the protein kinase domain of the Egfr protein between amino acids 771 and 772 (UniProt.org). N771_P772insRH has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other Egfr exon 20 insertions (PMID: 24353160).
K860I missense unknown EGFR K860I lies within the protein kinase domain of the Egfr protein (UniProt.org). K860I has been identified in the scientific literature (PMID: 26923333, PMID: 19536777, PMID: 21610522), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
H870Y missense unknown EGFR H870Y lies within the protein kinase domain of the Egfr protein (UniProt.org). H870Y has been identified in the scientific literature (PMID: 21070477, PMID: 25862146), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
T430S missense unknown EGFR T430S lies within the extracellular domain of the Egfr protein (UniProt.org). T430S has been identified in sequencing studies (J Clin Oncol 37, 2019 (suppl; abstr e13000)), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Jun 2019).
A289D missense gain of function EGFR A289D lies within the extracellular domain of the Egfr protein (PMID: 22588883). A289D confers a gain of function on Egfr protein, as indicated by increased Egfr phosphorylation (PMID: 22588883) and increased cell proliferation and viability in culture (PMID: 29533785).
S464L missense gain of function EGFR S464L lies within the extracellular domain of the Egfr protein (UniProt.org). S464L results in increased Egfr and Erk phosphorylation and confers resistance to Erbitux (cetuximab) and Vectibix (panitumumab) in cell culture (PMID: 26843189). Y
L747P missense unknown EGFR L747P lies within the protein kinase domain of the Egfr protein (UniProt.org). L747P has been associated with drug resistance (PMID: 26339441), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Apr 2019). Y
positive unknown unknown EGFR positive indicates the presence of the EGFR gene, mRNA, and/or protein.
N528D missense no effect - predicted EGFR N528D lies within the extracellular domain of the Egfr protein (UniProt.org). N528D results in similar cell proliferation and autophosphorylation as wild-type Egfr in culture (PMID: 28979142) and therefore, is predicted to have no effect on Egfr protein function.
Y1016H missense unknown EGFR Y1016H lies within a site in the Egfr protein important for interaction with PIK3C2B (UniProt.org). Y1016H has been identified in sequencing studies (PMID: 29106415), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
G719D missense unknown EGFR G719D lies within the P-loop in the kinase domain of the Egfr protein (PMID: 17349580). G719D results in increased transformation ability in one of two different cell lines in one study (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
V774L missense no effect - predicted EGFR V774L lies within the protein kinase domain of the Egfr protein (UniProt.org). V774L results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
K806A missense unknown EGFR K806A lies within the protein kinase domain of the Egfr protein (UniProt.org). K806A has been identified in the scientific literature (PMID: 19536777), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
R748I missense unknown EGFR R748I lies within the protein kinase domain of the Egfr protein (UniProt.org). R748I has been identified in the scientific literature (PMID: 29369805), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
exon21 unknown unknown EGFR exon 21 indicates an unspecified mutation has occurred in exon 21 of the EGFR gene.
E709_T710delinsD indel gain of function EGFR E709_T710delinsD results in a deletion of two amino acids in the protein kinase domain of the Egfr protein from aa 709 to aa 710, combined with the insertion of an aspartic acid (D) at the same location (UniProt.org). E709_T710delinsD confers a gain of function to Egfr, resulting in phosphorylation of the Egfr protein and transformation of cultured cells (PMID: 26206867, PMID: 29533785).
P772_H773dup insertion gain of function - predicted EGFR P772_H773dup (also referred to as H773_V774insPH) indicates the insertion of 2 duplicate amino acids, proline (P)-772 through histidine(H)-773, in the protein kinase domain of the Egfr protein (UniProt.org). P772_H773dup has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other EGFR exon 20 insertion mutations (PMID: 24353160).
S752I missense unknown EGFR S752I lies within the protein kinase domain of the Egfr protein (UniProt.org). S752I has been identified in the scientific literature (PMID: 17409862, PMID: 25411647), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
P772_H773insGNP insertion gain of function EGFR P772_H773insGNP (also referred to as D770_N771insNPG) results in the insertion of three amino acids in the protein kinase domain of the Egfr protein between amino acids 772 and 773 (UniProt.org). P772_H773insGNP (D770_N771insNPG) results in increased Egfr kinase activity and is transforming in culture (PMID: 24353160).
E866K missense loss of function EGFR E866K lies within the protein kinase domain of the Egfr protein (UniProt.org). E866K results in a loss of Egfr kinase activity and is not transforming in cell culture (PMID: 19147750).
K261* nonsense unknown EGFR K261* results in a premature truncation of the Egfr protein at amino acid 261 of 1210 (UniProt.org). The functional effect of K261* is conflicting, as K261* demonstrates greater than 24.5-fold growth advantage in IL-3-depeleted cells in culture, as compared to wild-type Egfr (PMID: 30952700), however loss of the majority of all known functional domains predicts a loss of function on the Egfr protein.
G719S missense gain of function EGFR G719S lies within the phosphate-binding “P loop” in the protein kinase domain of the Egfr protein (PMID: 17349580). G719S results in constitutive ligand-independent phosphorylation of Egfr, activation of Stat5, Erk1/2, and Akt, and is transforming in cell culture (PMID: 16204070, PMID: 24894453, PMID: 18573086, PMID: 29533785).
T847I missense unknown EGFR T847I lies within the protein kinase domain of the Egfr protein (Uniprot.org). T847I has been identified in the scientific literature (PMID: 24743239, PMID: 21457545, PMID: 23800712), but has not been biochemically characterized and therefore its effect on Egfr protein is unknown (PubMed, Mar 2019).
G696_P1033dup duplication gain of function EGFR G696_P1033dup indicates the tandem duplication of exons 18 through 25 of EGFR, resulting in duplication of the kinase domain (PMID: 26286086). G696_P1033dup results in constitutive activation of Egfr and a dramatic increase in colony formation relative to L858R in culture (PMID: 26286086).
H850D missense unknown EGFR H850D lies within the protein kinase domain of the Egfr protein (UniProt.org). H850D has been identified in the scientific literature (PMID: 19060236, PMID: 18509184), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
V159E missense no effect - predicted EGFR V159E lies within the extracellular domain of the Egfr protein (UniProt.org). V159E results in similar cell proliferation and autophosphorylation as wild-type Egfr in culture (PMID: 28979142) and therefore, is predicted to have no effect on Egfr protein function.
D855G missense loss of function - predicted EGFR D855G lies within the protein kinase domain of the Egfr protein (UniProt.org). D855G results in a loss of Egfr kinase activity in cell culture in one study (PMID: 26101090) and therefore, is predicted to lead to a loss of Egfr protein function.
D770_P772dup insertion gain of function - predicted EGFR D770_P772dup (also referred to as P772_H773insDNP) indicates the insertion of 3 duplicate amino acids, aspartic acid (D)-770 through proline (P)-772, in the protein kinase domain of the Egfr protein (UniProt.org). D770_P772dup has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other Egfr exon 20 insertions (PMID: 24353160).
C797S missense unknown EGFR C797S lies within the ATP-binding pocket in the protein kinase domain of the Egfr protein (PMID: 25964297). The functional effect of C797S is conflicting, as C797S demonstrated greater than 24.5-fold growth advantage in IL-3-depeleted cells in culture, as compared to wild-type Egfr (PMID: 30952700), but in another assay in the same study, C797S did not induce cell proliferation in the absence of IL-3 (PMID: 30952700), but has been demonstrated to confer resistance to third-generation EGFR inhibitors (PMID: 25964297, PMID: 25948633, PMID: 29410323). Y
E114K missense no effect - predicted EGFR E114K lies within the cytoplasmic domain of the Egfr protein (UniProt.org). E114K results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
H304Y missense gain of function - predicted EGFR H304Y lies within the extracellular domain of the Egfr protein (UniProt.org). H304Y results in increased transformation ability in two different cell lines in one study (PMID: 29533785) and therefore, is predicted to lead to a gain of Egfr protein function.
L38V missense no effect - predicted EGFR L38V lies within the extracellular domain of the Egfr protein (UniProt.org). L38V results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
L730F missense unknown EGFR L730F lies within the protein kinase domain of the Egfr protein (UniProt.org). L730F has been identified in the scientific literature (PMID: 16014883, PMID: 23244191), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
negative unknown loss of function EGFR negative indicates a lack of the EGFR gene, mRNA, and/or protein.
E709V missense unknown EGFR E709V lies within the cytoplasmic domain of the Egfr protein (UniProt.org). E709V has been identified in the scientific literature (PMID: 18036700, PMID: 22776705, PMID: 23242437), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
I706T missense unknown EGFR I706T lies within the protein kinase domain of the Egfr protein (UniProt.org). I706T has been identified in the scientific literature (PMID: 17575133, PMID: 25521408), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
N771delinsFH indel gain of function - predicted EGFR N771delinsFH results in a deletion of asparagine (N) at amino acid 771 within the protein kinase domain of the Egfr protein, combined with the insertion of a phenylalanine (F) and a histidine (H) at the same site (UniProt.org). N771delinsFH has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other Egfr exon 20 insertions (PMID: 24353160).
Q181H missense no effect - predicted EGFR Q181H lies within the extracellular domain of the Egfr protein (UniProt.org). Q181H results in similar cell proliferation and autophosphorylation as wild-type Egfr in culture (PMID: 28979142) and therefore, is predicted to have no effect on Egfr protein function.
exon19 unknown unknown EGFR exon 19 indicates an unspecified mutation has occurred in exon 19 of the EGFR gene.
K708M missense no effect - predicted EGFR K708M lies within the cytoplasmic domain of the Egfr protein (UniProt.org). K708M results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
P546S missense unknown EGFR P546S lies within the extracellular domain of the Egfr protein (UniProt.org). P546S demonstrates protein expression and cellular localization similar to wild-type Egfr (PMID: 23578570), but also results in increased cell proliferation and cell viability as compared to wild-type Egfr in one of two different cell lines in culture (PMID: 29533785), and therefore, its effect on Egfr protein function is unknown.
A702S missense unknown EGFR A702S lies within a region of the Egfr protein important for dimerization, phosphorylation, and activation (UniProt.org). A702S decreased cell proliferation and cell viability as compared to wild-type Egfr in one of two cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Apr 2019).
L844V missense no effect - predicted EGFR L844V lies within the protein kinase domain of the Egfr protein (UniProt.org). L844V is predicted to have no effect on Egfr protein function as indicated by a lack of transforming ability in culture in one study, and is associated with resistance to third-generation Egfr inhibitors (PMID: 25948633). Y
G721S missense unknown EGFR G721S lies within the protein kinase domain of the Egfr protein (UniProt.org). G721S has been identified in the scientific literature (PMID: 17192902, PMID: 21057220), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
S229C missense gain of function - predicted EGFR S229C lies within the extracellular domain of the Egfr protein (UniProt.org). S229C results in increased transformation ability in two different cell lines in one study (PMID: 29533785) and therefore, is predicted to lead to a gain of Egfr protein function.
R252P missense gain of function - predicted EGFR R252P lies within the extracellular domain of the Egfr protein (UniProt.org). R252P results in increased transformation ability in two different cell lines in one study (PMID: 29533785) and therefore, is predicted to lead to a gain of Egfr protein function.
R324L missense no effect - predicted EGFR R324L lies within the extracellular domain of the Egfr protein (UniProt.org). R324L results in similar cell proliferation and autophosphorylation as wild-type Egfr in culture (PMID: 28979142) and therefore, is predicted to have no effect on Egfr protein function.
T751fs frameshift loss of function - predicted EGFR T751fs results in a change in the amino acid sequence of the Egfr protein beginning at aa 751 of 1210, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), T751fs is predicted to lead to a loss of Egfr protein function.
EGFR - RAD51 fusion gain of function EGFR-RAD51 results from the fusion of EGFR and RAD51, demonstrating activation of downstream signaling pathways, MAPK and PI3K, transformation activity in culture, and increased colony formation (PMID: 27102076). EGFR-RAD51 has been identified in lung cancer (PMID: 27102076, PMID: 31064887).
V769_D770insERG insertion gain of function - predicted EGFR V769_D770insERG results in the insertion of three amino acids in the protein kinase domain of the Egfr protein between amino acids 769 and 770 (UniProt.org). V769_D770insERG has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other Egfr exon 20 insertions (PMID: 24353160).
S752Y missense unknown EGFR S752Y lies within the protein kinase domain of the Egfr protein (UniProt.org). S752Y has been identified in the scientific literature (PMID: 29575851), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Mar 2019).
D770_N771insG insertion gain of function - predicted EGFR D770_N771insG results in the insertion of a glycine (G) in the protein kinase domain of the Egfr protein between amino acids 770 and 771 (UniProt.org). D770_N771insG has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other Egfr exon 20 insertions (PMID: 16187797).
T625A missense no effect - predicted EGFR T625A lies within the extracellular domain of the Egfr protein (UniProt.org). T625A results in similar cell proliferation and viability levels as wild-type Egfr in culture in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
A767V missense unknown EGFR A767V lies within the protein kinase domain of the Egfr protein (UniProt.org). A767V has been identified in the scientific literature (PMID: 26066407, PMID: 24040454), but not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019).
L747_T751delinsS indel gain of function - predicted EGFR L747_T751delinsS results in a deletion of five amino acids in the protein kinase domain of the Egfr protein from aa 747 to aa 751, combined with the insertion of serine (S) at the same site (UniProt.org). L747_T751delinsS has not been biochemically characterized, but is predicted to result in a gain of function based on the effect of other EGFR exon 19 deletion and deletion-insertion mutations (PMID: 19147750, PMID: 22190593, PMID: 23387505).
E865K missense unknown EGFR E865K lies within the protein kinase domain of the Egfr protein (UniProt.org). E865K has been demonstrated to confer resistance to some EGFR inhibitors (PMID: 29141884), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Feb 2019). Y
L62R missense unknown EGFR L62R lies within the extracellular domain of the Egfr protein (UniProt.org). L62R results in increased cell proliferation and cell viability as compared to wild-type Egfr in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown.
Molecular Profile Protein Effect Treatment Approaches
EGFR V786M unknown
EGFR G724S EGFR E746_S752delinsV EGFR T790M
EGFR G724S gain of function Cetuximab
EGFR E734K unknown
EGFR P1202Q unknown
EGFR H773L EGFR V774M
EGFR V774M unknown
EGFR H870R gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR D770_N771insNPY gain of function - predicted
EGFR E746_T751delinsA unknown
EGFR E734Q gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR V769M gain of function - predicted
EGFR S921R unknown
EGFR D191N no effect - predicted
EGFR D612N no effect - predicted
EGFR D994Y unknown
EGFR act mut gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR C797S EGFR act mut
EGFR act mut EGFR amp
EGFR act mut MET amp
EGFR T790M EGFR act mut PIK3CA E545K
EGFR T790M EGFR act mut EGFR amp
EGFR act mut EGFR C797S EGFR T790M
EGFR act mut EGFR T790M MET amp
EGFR T790M EGFR act mut ERBB2 amp
EGFR T790M EGFR act mut PIK3CA E542K
EGFR amp EGFR wild-type EGFR act mut
EGFR amp EGFR act mut PTEN R308C
EGFR act mut EGFR A289T PTEN I253N PTEN N69D
EGFR act mut EGFR T790M
EGFR-YAP1 unknown
EGFR E967A unknown
EGFR L633F no effect - predicted
EGFR E746_T751delinsV gain of function - predicted
EGFR R108G gain of function - predicted
EGFR V769_D770insMASVD gain of function - predicted
EGFR E690K no effect - predicted
EGFR L861F unknown
EGFR Y125C unknown
EGFR D956V no effect - predicted
EGFR exon 19 del EGFR exon 19 ins
EGFR exon 19 ins gain of function
EGFR G721A unknown
EGFR L858R EGFR T854A EGFR Inhibitor 3rd gen
EGFR C797S EGFR L858R EGFR T854A
EGFR T854A unknown
EGFR C797S EGFR exon 19 del EGFR T854A
EGFR exon 19 del EGFR T854A
EGFR E709K EGFR L858R
EGFR E709K gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan) Neratinib
EGFR G796S gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR G874S unknown
EGFR T302H unknown
EGFR A871V unknown
EGFR Q1159R unknown
EGFR V738G unknown
EGFR K806E unknown
EGFR S198R no effect - predicted
EGFR G719fs loss of function - predicted
EGFR I941R loss of function
EGFR I941R EGFR L858R EGFR T790M
EGFR T790M EGFR L858R EGFR A871G TP53 R248W RB1 K844S
EGFR A871G gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR G873Q unknown
EGFR P281T unknown
EGFR P959fs unknown
EGFR R776C gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR fusion unknown
EGFR K728* unknown
EGFR S116F no effect - predicted
EGFR D770_N771insAPW gain of function - predicted
EGFR G598A no effect - predicted
EGFR D1014V unknown
EGFR M178I unknown
EGFR P589L unknown
EGFR I821T unknown
EGFR-ZNF713 unknown
EGFR E746_T751del gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR T34_A289del gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR E746_S752del EGFR T790M EGFR P794L
EGFR P794L unknown
EGFR T790M EGFR G796R EGFR L858R
EGFR G796R unknown
EGFR T790M EGFR G796R
EGFR amp EGFR E746_A750del
EGFR amp no effect EGFR Antibody EGFR Inhibitor (Pan) HER inhibitor (Pan)
EGFR amp EGFR G696_P1033dup
EGFR amp ERBB2 amp MET amp
EGFR amp EGFR G719A
PDGFRA amp EGFR amp
EGFR amp ERBB2 over exp
EGFR amp FGFR1 amp
EGFR amp EGFR over exp
EGFR amp MET amp
EGFR amp EGFR E746_A750del EGFR T790M
EML4-ALK EGFR amp
EGFR amp EGFR S492R BRAF V600E
EGFR amp ERBB2 pos
EGFR amp EGFR S492R
EGFR amp ERBB2 amp
BRAF V600E EGFR amp
EGFR amp PTEN loss
EGFR D770_N771insGF gain of function - predicted
EGFR G42D no effect - predicted
EGFR V851I unknown
EGFR K721M loss of function
EGFR F48Y unknown
EGFR R451C loss of function - predicted
EGFR H850Y unknown
EGFR E746K gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR D761Y EGFR L858R EGFR Inhibitor 3rd gen
EGFR D761Y unknown
EGFR L747_A755delinsSRD gain of function - predicted
EGFR A216T EGFR E746_S752delinsV
EGFR A216T unknown
EGFR G857E unknown
EGFR L747_T751del EGFR S752I
EGFR L747_T751del gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR P1059R no effect - predicted
EGFR T263I unknown
EGFR exon 20 ins gain of function
EGFR V769_N771dup gain of function - predicted
EGFR R831C no effect - predicted
EGFR L747_E749del gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR A750P EGFR L747_E749del PIK3CA E545K
EGFR A750P EGFR L747_E749del
EGFR Q701* loss of function - predicted
EGFR A237F unknown
EGFR T854S unknown
EGFR P622S unknown
EGFR V765G unknown
EGFR A767T gain of function - predicted
EGFR E746_T751delinsL gain of function - predicted
EGFR T354K unknown
EGFR E804G EGFR P699L
EGFR E804G gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR L747_S752del EGFR T790M
EGFR L747_S752del gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR F712S unknown
EGFR K757R unknown
EGFR D770_N771insGD gain of function - predicted
EGFR L747* loss of function - predicted
EGFR I744M unknown
EGFR K739_I744dup gain of function
EGFR K714R unknown
EGFR K714R EGFR L858R
EGFR S720Y unknown
EGFR S380Pfs*16 loss of function - predicted
EGFR Q52R unknown
EGFR D770_N771insGV gain of function - predicted
EGFR P596R unknown
EGFR E746_A750del EML4-ALK
EGFR E746_A750del EGFR T790M EGFR Q791R
EGFR E746_A750del EGFR T790M EGFR C797S
EGFR E746_A750del EGFR L844V
EGFR E746_A750del FGFR3-TACC3
EGFR E746_A750del gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
BRAF V600E EGFR E746_A750del
EGFR E746_A750del EGFR T790M EGFR L844V
EGFR E746_A750del EGFR L718Q
EGFR E746_A750del EGFR T790M
EGFR E746_A750del MET amp
EGFR E746_A750del SMO amp
EGFR E746_A750del EGFR T790M EGFR L718Q
EGFR E746_A750del EGFR C797S
EGFR E746_A750del EGFR L792F
EGFR G810S gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR exon 19 del NRAS Q61K
EGFR exon 19 del MET amp
EGFR exon 19 del MET amp MET D1228V
EGFR exon 19 del TP53 exon8
EGFR exon 19 del EGFR K754E
EGFR exon 19 del ERBB2 wild-type
EGFR exon 19 del gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR exon 19 del NRAS G12R
EGFR exon 19 del TP53 wild-type
EGFR C797S EGFR exon 19 del
EGFR exon 19 del BRAF V600E
EGFR exon 19 del EGFR S645C
EGFR exon 19 del NRAS G12V
EGFR exon 19 del EGFR T790M
EGFR C797S EGFR exon 19 del EGFR T790M
EGFR exon 19 del EGFR T790M EGFR L798I
EGFR exon 19 del EGFR T790M MET amp
EGFR exon 19 del EGFR T790M NRAS Q61K
BRAF V600E EGFR exon 19 del MET amp
EGFR exon 19 del PTEN mut
EGFR exon 19 del NRAS E63K
EGFR exon 19 del PIK3CA E418K PIK3CA E542K
EGFR exon 19 del NRAS amp
EGFR exon 19 del MET act mut
EGFR K745_E746insTPVAIK gain of function
EGFR A289T EGFR L858R
EGFR A289T unknown
EGFR R831L unknown
EGFR T751_I759del gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR D807N unknown
EGFR A864T unknown
EGFR dec exp no effect
EGFR C775Y unknown
EGFR S492R unknown Afatinib Osimertinib
EGFR P733L unknown
EGFR V834M unknown
EGFR G863D no effect - predicted
EGFR E709A EGFR G719S
EGFR E709A gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan) Neratinib
EGFR E709A EGFR G719C
EGFR E709A EGFR L858R
EGFR L792F EGFR L858R
EGFR L792F unknown
EGFR E709_T710delinsD EGFR L792F
EGFR L814P unknown
EGFR D761G unknown
EGFR S768T unknown
EGFR G465E EGFR G465R
BRAF V600E EGFR G465R
EGFR G465R gain of function
EGFR G465R EGFR S464L
EGFR A508V no effect - predicted
EGFR G573* loss of function - predicted
EGFR E758G unknown
EGFR R776G gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR M277E gain of function
EGFR L704N loss of function
EGFR G721D unknown
EGFR A763_Y764insFQEA gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR L858R EGFR E884K
EGFR E884K unknown
EGFR P848L unknown
EGFR exon20 unknown
EGFR G588S unknown
EGFR L718P unknown
EGFR P772_H773insPNP gain of function - predicted
EGFR S752_I759del gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR D770_N771insY gain of function - predicted
EGFR G983R gain of function - predicted
EGFR A613T unknown
EGFR L798I unknown
EGFR R832H unknown
EGFR C797G loss of function
EGFR E746_P753delinsVS gain of function - predicted
EGFR H773_V774insAH gain of function - predicted
EGFR N771_H773dup gain of function
EGFR G857R unknown
EGFR L858R EGFR L718Q EGFR T790M
EGFR L858R gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan) Cetuximab
EGFR L858R NRAS mut
EGFR L858R EGFR Q791R EGFR T790M
EGFR L858R EGFR L844V
EGFR T790M EGFR L858R EGFR L792H
EGFR L858R EGFR L844V EGFR T790M
EGFR L858R EML4-ALK
EGFR L858R EGFR S306L
EGFR L858R EGFR T790M MET amp
EGFR L858R FGFR3-TACC3
EGFR L703I EGFR L858R
EGFR E709G EGFR L858R
EGFR L858R EGFR T790M PIK3CA G118D
EGFR C797S EGFR L792H EGFR L858R
EGFR L858R EGFR R108K
EGFR G719X EGFR S768I EGFR T790M EGFR L858R EGFR L861Q
EGFR L858R EGFR T790M MET amp MET D1228H D1228N D1231Y Y1230H
EGFR T790M EGFR L858R EGFR over exp
EGFR L858R EGFR T790M MET amp MET D1231Y
EGFR L858R EGFR V765_M766delinsHH
EGFR T790M EGFR L858R ERBB2 over exp
EGFR L858R EGFR T790M EGFR Inhibitor 3rd gen
EGFR C797S EGFR L858R EGFR T790M
EGFR L858R EGFR L718Q
EGFR L858R EGFR L747S
EGFR L858R EGFR C797S
EGFR L858R EGFR V292L
EGFR L858R EGFR T790M NRAS Q61K
ALK amp EML4-ALK EGFR L858R
EGFR L858R MET amp
EGFR-FGFR1 EGFR L858R
EGFR E709V EGFR L858R
EGFR L858R PTEN mut
EGFR V802I unknown
EGFR L747_A750del gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR L798H unknown
EGFR N826S unknown
EGFR T751I unknown
EGFR G719C gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan) Neratinib
EGFR M766_A767insAA gain of function - predicted
EGFR A750P unknown
EGFR V292M unknown
EGFR L833* unknown
EGFR-PURB unknown Erlotinib
EGFR R108K gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR K754H unknown
EGFR L718Q no effect - predicted
EGFR Q432R unknown
EGFR K737E no effect - predicted
EGFR G810D unknown
EGFR R831H gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR T751_I759delinsN gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR A750V unknown
EGFR K467T gain of function
EGFR S768N no effect
EGFR G312W unknown
EGFR R1052K unknown
EGFR M137K unknown
EGFR A289V gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR H773dup gain of function
EGFR K467X unknown
EGFR V1133M unknown
EGFR E709X unknown
EGFR L838M no effect - predicted
EGFR V769_D770insGVV gain of function - predicted
EGFR G719A EGFR L861Q EGFR T790M
EGFR G719S EGFR L861Q
EGFR G719A EGFR L861Q
EGFR L861Q gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR I475V no effect - predicted
EGFR P596S gain of function - predicted
EGFR mut TP53 mut
EGFR mutant unknown
EGFR mut MET mut
EGFR mut TP53 inact mut
EGFR mut MET amp
EGFR mut TP53 exon 8
EGFR T790M EGFR mut
EGFR mutant FGFR1 wild-type
EGFR V851A loss of function
EGFR E513D no effect - predicted
EGFR E709H unknown
EGFR P794S no effect - predicted
EGFR R252C no effect - predicted
EGFR S720C unknown
EGFR H773_V774dup gain of function - predicted
EGFR T402S unknown
EGFR A1118T unknown
EGFR L833V gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR L833V EGFR H835L
EGFR I213M unknown
EGFR R776S unknown
EGFR L858K unknown
EGFR R1052I unknown
EGFR D1009N no effect - predicted
EGFR V765L unknown
EGFR R98Q no effect - predicted
EGFR P733S unknown
EGFR Q787R gain of function - predicted
EGFR D770_N771insSVD gain of function - predicted
EGFR V765A unknown
EGFR R889G unknown
EGFR E709G gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan) Neratinib
EGFR P373Q no effect - predicted
EGFR S784Y unknown
EGFR I1018N unknown
EGFR R803W unknown
EGFR L838V gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR L1087P no effect - predicted
EGFR G735A unknown
EGFR N771dup gain of function - predicted
EGFR L747_A750delinsP gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR L747_A750delinsP FGFR3-TACC3
EGFR E746_A750delinsIP gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR-PPARGC1A gain of function
EGFR T790M EGFR L792H
EGFR L792H unknown
EGFR V769_D770insGSV gain of function - predicted
EGFR G779S unknown
EGFR E45Q no effect - predicted
EGFR T363I gain of function - predicted
EGFR L90F unknown
EGFR T725M gain of function
EGFR S1153I unknown
EGFR D770delinsGY EGFR T790M
EGFR D770delinsGY EGFR C797S
EGFR D770delinsGY gain of function Dacomitinib
EGFR L688P loss of function
EGFR L792P unknown
EGFR R222C gain of function - predicted Afatinib Osimertinib
EGFR A120P unknown
EGFR V769L gain of function - predicted
EGFR G696E unknown
EGFR K593Q unknown
EGFR R677H unknown
EGFR H988P unknown
EGFR G735S unknown
EGFR loss loss of function
EGFR N700D unknown
EGFR A698T unknown
EGFR-FGFR1 unknown
EGFR E868G unknown
EGFR V843L unknown
EGFR V148M unknown
EGFR A702V gain of function - predicted
EGFR V592I no effect
EGFR V765_M766delinsHH unknown
EGFR D256Y unknown
EGFR V292L unknown
EGFR S768I gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR I740_K745dup gain of function - predicted
EGFR T790M MET amp
EGFR G719S EGFR T790M
EGFR T790M ERBB2 over exp
EGFR L747_T751delinsP EGFR T790M
EGFR C797S EGFR P772_H773insGNP EGFR T790M
EGFR P772_H773insGNP EGFR T790M
EGFR T790M gain of function EGFR Inhibitor 3rd gen PF-06747775
EGFR C797S EGFR T790M
EGFR L747_P753delinsS + EGFR T790M
EGFR C797S EGFR L747_P753delinsS EGFR T790M
EGFR G719A EGFR T790M
EGFR E709Q unknown
EGFR V742A unknown
EGFR L792_M793insHIV gain of function - predicted
EGFR D368Y unknown
EGFR E868V unknown
EGFR D770N unknown
EGFR L858Q unknown
EGFR D770_N771insGL gain of function - predicted
EGFR Q791R unknown
EGFR I491M gain of function
EGFR E746_S752delinsV gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR E746_S752delinsV MET-UBE2H
EGFR A839V unknown
EGFR E282K no effect - predicted
EGFR A864V unknown
EGFR D770_N771insSVE gain of function - predicted
EGFR del loss of function
EGFR D761_E762insEAFQ gain of function - predicted
EGFR R841K unknown
EGFR K754E gain of function
EGFR A859T unknown
EGFR H773L unknown
EGFR L747_P753delinsS gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR L747_P753delinsS EML4-ALK
EGFR A767_V769dup gain of function
EGFR P753S unknown
EGFR P1170H unknown
EGFR E561K unknown
EGFR L692P unknown
EGFR P596L gain of function - predicted Afatinib Osimertinib
EGFR A743T unknown
EGFR V769_D770insASV gain of function - predicted
EGFR K745M loss of function
EGFR N444S unknown
EGFR K745_E749del gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR G719X unknown EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan) Neratinib
EGFR T263P gain of function
EGFR H773Y unknown
EGFR S784F unknown
BRAF D594N BRAF G466A EGFR over exp MET over exp
EGFR over exp FGFR1 over exp
EGFR over exp + ERBB2 wild type
EGFR over exp ERBB2 dec exp
EGFR over exp PIK3CA E542K
EGFR over exp FGFR2 amp
BRAF V600E EGFR over exp
EGFR over exp no effect
EGFR over exp FGFR1 amp
EGFR V689M gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR A871T no effect - predicted
EGFR F712L no effect - predicted
EGFR G465E gain of function
EGFR H47Y unknown
EGFR P772R gain of function - predicted
EGFR T751_E758del gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR F795L unknown
EGFR A763V unknown
EGFR S752F unknown
EGFR S784P unknown
EGFR S645C gain of function
EGFR S752P unknown
EGFR H773R unknown
EGFR S720P unknown
EGFR K745_A750del gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR H773_V774insQ gain of function - predicted
EGFR G810A unknown
EGFR P272L loss of function - predicted
EGFR Q1164R no effect - predicted
EGFR D770_N771insGT gain of function - predicted
EGFR F712Y unknown
EGFR I853T loss of function
EGFR L861R gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR L833F unknown
EGFR T354M unknown
EGFR Q105H unknown
EGFR L703P unknown
EGFR L858M unknown
EGFR L747_P753delinsQ gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR P741L unknown
EGFR V843I gain of function
EGFR V765M unknown
EGFR D1072E no effect - predicted
EGFR N604I unknown
EGFR H835L unknown
EGFR T783A unknown
EGFR S720F unknown
EGFR D770_N771insMATP gain of function - predicted
EGFR S306L unknown
EGFR E746_S752del gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR P699L loss of function - predicted
EGFR R675Q unknown
EGFR E746_T751delinsVA gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR V834L unknown
EGFR L747_T751delinsP gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR L747_T751delinsP EML4-ALK
EGFR P699S unknown
EGFR D761N gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR G873E unknown
EGFR S220P no effect - predicted
EGFR K745R loss of function - predicted
EGFR Y764_V765insHH gain of function - predicted Afatinib Naquotinib Osimertinib
EGFR T710del unknown
EGFR wild-type MET wild-type
EGFR wild-type no effect
BRAF G466V EGFR wild-type
ALK wild-type EGFR wild-type
EGFR wild-type MET over exp
EGFR wild-type STK11 wild-type TP53 mut
EGFR R776H gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR D587H gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR M766_A767insAI gain of function - predicted
EGFR S498I unknown
EGFR G598V gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR L703I unknown
EGFR W731* loss of function - predicted
EGFR G721C unknown
EGFR T363N no effect - predicted
EGFR G779F unknown
EGFR R521K unknown
EGFR R521K FGFR2 M186T KDR Q472H KDR V297I RET M1009T
EGFR S768_D770dup gain of function - predicted
EGFR L747S gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR K745_E746insVPVAIK gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR G719A gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan) Neratinib
EGFR G719A EGFR I706T
EGFR P772_H773insPHA gain of function - predicted
EGFR A755G unknown
EGFR E746_E749del gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR F254I unknown
EGFR F856_G857insYIV unknown
EGFR-SEPTIN14 gain of function
EGFR A702T unknown
EGFR I740_P741insIHR gain of function - predicted
EGFR N771_P772insRH gain of function - predicted
EGFR K860I unknown
EGFR H870Y unknown
EGFR T430S unknown
EGFR A289D gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR S464L gain of function
EGFR L747P unknown
EGFR positive unknown
EGFR pos ERBB2 pos
EGFR N528D no effect - predicted
EGFR Y1016H unknown
EGFR G719D unknown EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan) Neratinib
EGFR V774L no effect - predicted
EGFR K806A unknown
EGFR R748I unknown
EGFR exon21 unknown
EGFR E709_T710delinsD gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR E709_T710delinsD SMAD4 R361C TP53 loss
EGFR E709_T710delinsD SMAD4 R361C
EGFR P772_H773dup gain of function - predicted
EGFR S752I unknown
EGFR P772_H773insGNP gain of function
EGFR E866K loss of function
EGFR K261* unknown
MAP2K1 Q56P MAP2K1 H119Y MAP2K1 D351G EGFR G719S
EGFR G719S gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan) Neratinib
EGFR G719S EGFR L62R
EGFR T847I unknown
EGFR G696_P1033dup gain of function
EGFR H850D unknown
EGFR V159E no effect - predicted
EGFR D855G loss of function - predicted
EGFR D770_P772dup gain of function - predicted
EGFR C797S unknown
EGFR E114K no effect - predicted
EGFR H304Y gain of function - predicted
EGFR L38V no effect - predicted
EGFR L730F unknown
EGFR neg FGFR1 over exp
EGFR negative loss of function
EGFR E709V unknown
EGFR I706T unknown
EGFR N771delinsFH gain of function - predicted
EGFR Q181H no effect - predicted
EGFR exon19 unknown
EGFR K708M no effect - predicted
EGFR P546S unknown
EGFR A702S unknown
EGFR L844V no effect - predicted
EGFR G721S unknown
EGFR S229C gain of function - predicted
EGFR R252P gain of function - predicted
EGFR R324L no effect - predicted
EGFR T751fs loss of function - predicted
EGFR-RAD51 gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan) Cetuximab
EGFR V769_D770insERG gain of function - predicted
EGFR S752Y unknown
EGFR D770_N771insG gain of function - predicted
EGFR T625A no effect - predicted
EGFR A767V unknown
EGFR L747_T751delinsS gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR E865K unknown
EGFR L62R unknown
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
EGFR V786M Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR V786M were sensitive to treatment with Gilotrif (afatinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR V786M Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR V786M were sensitive to treatment with Tagrisso (osimertinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR G724S EGFR E746_S752delinsV EGFR T790M lung adenocarcinoma predicted - resistant Osimertinib Case Reports/Case Series Actionable In a clinical case study, a single patient with lung adenocarcinoma harboring an EGFR exon 19 deletion (E746_S752delinsV) and EGFR T790M was found to have acquired, via cell free DNA testing, an EGFR G724S mutation upon disease progression after 1 year of Tagrisso (osimertinib) therapy (PMID: 30588029). 30588029
EGFR H773L EGFR V774M lung adenocarcinoma predicted - resistant Afatinib Case Reports/Case Series Actionable In a clinical case study, a patient with lung adenocarcinoma harboring EGFR H773L and EGFR V774M demonstrated rapid progression following first-line treatment with Gilotrif (afatinib) (PMID: 31007929). 31007929
EGFR V774M Advanced Solid Tumor resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR V774M were resistant to treatment with Tarceva (erlotinib) in culture (PMID: 29141884). 29141884
EGFR V774M Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR V774M were sensitive to treatment with Tagrisso (osimertinib) in culture (PMID: 29141884). 29141884
EGFR V774M Advanced Solid Tumor sensitive Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR V774M were sensitive to treatment with Erbitux (cetuximab) in culture (PMID: 29141884). 29141884
EGFR V774M Advanced Solid Tumor resistant Gefitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR V774M were resistant to treatment with Iressa (gefitinib) in culture (PMID: 29141884). 29141884
EGFR D770_N771insNPY lung non-small cell carcinoma predicted - sensitive Luminespib Phase II Actionable In a Phase II trial, Luminespib (AUY922) treatment demonstrated safety and efficacy in patients with advanced non-small cell lung cancer harboring EGFR exon 20 insertions, with 1 patient harboring EGFR D770_N771insNPY achieved stable disease (PMID: 30351341; NCT01854034). 30351341
EGFR E734Q Advanced Solid Tumor sensitive Erlotinib Preclinical Actionable In a preclinical study, cells expressing EGFR E734Q demonstrated sensitivity to Tarceva (erlotinib) in culture (PMID: 20942962). 20942962
EGFR V769M Advanced Solid Tumor sensitive Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR V769M were sensitive to treatment with Erbitux (cetuximab) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR V769M Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR V769M were sensitive to treatment with Gilotrif (afatinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR V769M Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR V769M were sensitive to treatment with Tagrisso (osimertinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR V769M Advanced Solid Tumor resistant Rociletinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR V769M were resistant to treatment with Rociletinib (CO-1686) in culture (PMID: 29141884). 29141884
EGFR V769M lung non-small cell carcinoma decreased response Icotinib Clinical Study Actionable In a retrospective analysis, non-small cell lung cancer patients harboring EGFR V769M demonstrated a response rate of 0% and disease control rate of 100%, and a median progression-free survival of 3.2 months following treatment with icotinib (J Clin Oncol 35, 2017 (suppl; abstr e14050)). detail...
EGFR act mut lung non-small cell carcinoma sensitive Osimertinib Guideline Actionable Tagrisso (osimertinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring sensitizing EGFR activating mutations (PMID: 30715168, PMID: 30285222; ESMO.org). 30285222 detail... 30715168
EGFR act mut lung non-small cell carcinoma no benefit Erlotinib + MK2206 Phase II Actionable In a Phase II trial, non-small cell lung cancer patients harboring EGFR activating mutations treated with Tarceva (erlotinib), in combination with MK-2206, demonstrated a 9% (4/45) response rate, which did not reach the primary endpoint rate of 20% or more, therefore, indicating no benefit (PMID: 26106072). 26106072
EGFR act mut lung non-small cell carcinoma sensitive Sapitinib Preclinical - Cell line xenograft Actionable In a preclinical study, Sapitinib (AZD8931) inhibited EGFR, ERBB2, and ERBB3 kinase activity, and inhibited growth in several non-small cell lung cancer cell lines and xenograft models, including those with EGFR activating mutations (PMID: 20145185). 20145185
EGFR act mut lung non-small cell carcinoma decreased response Neratinib Phase I Actionable In a Phase I trial, Nerlynx (neratinib) demonstrated limited clinical activity in EGFR-mutant non-small cell lung cancer patients with prior EGFR TKI therapy, with a response rate of 3.4% (3/88), stable disease as best response in 50% (44/88), and prolonged stable disease in 10%, (9/88) (PMID: 20479403). 20479403
EGFR act mut lung non-small cell carcinoma sensitive Amlexanox + Selumetinib Preclinical - Cell line xenograft Actionable In a preclinical study, non-small cell lung cancer cell lines harboring activating EGFR mutations demonstrated sensitivity to the combination of amlexanox and Selumetinib (AZD6244), resulting in synergistic growth inhibition in culture and reduced tumor growth in xenograft models (PMID: 27287717). 27287717
EGFR act mut lung non-small cell carcinoma no benefit Erlotinib + Luminespib Phase Ib/II Actionable In a Phase Ib/II clinical trial, the combination of Luminespib (AUY922) and Tarceva (erlotinib) demonstrated limited clinical benefit in patients with EGFR-mutant non-small cell carcinoma with acquired resistance to EGFR tyrosine kinase inhibitors, with 16% (4/25) patients achieving partial response (PMID: 25870087). 25870087
EGFR act mut lung non-small cell carcinoma sensitive Naquotinib Phase I Actionable In a Phase I trial, ASP8273 demonstrated preliminary antitumor activity in non-small cell lung patients harboring EGFR activating mutations (J Clin Oncol 33, 2015 (suppl; abstr 8014). detail...
EGFR act mut lung non-small cell carcinoma sensitive Afatinib Phase II Actionable In a Phase II trial, Gilotrif (afatinib) treatment, when compared to Iressa (gefitinib), resulted in statistically significant improvement of progression free survival (11.0 vs 10.9 months, HR 0.74, p=0.0178), time-to-treatment failure (13.7 vs 11.5 months, HR 0.75, p=0.0136), and objective response rate (72.5% vs 56%, odd ratio 2.121, p=0.0018) in patients harboring EGFR L858R or exon 19 deletion activating mutations (PMID: 28169392). 28169392
EGFR act mut lung non-small cell carcinoma sensitive Afatinib Guideline Actionable Gilotrif (afatinib) is included in guidelines as first-line therapy for patients with metastatic non-small cell lung cancer harboring sensitizing EGFR activating mutations (PMID: 30715168, PMID: 30285222; ESMO.org). detail... 30285222 30715168
EGFR act mut Advanced Solid Tumor predicted - sensitive ABT-806 Phase I Actionable In a Phase I trial, ABT-806 treatment in patients with advanced solid tumors that often express EGFR amplification or EGFR vIII was well-tolerated, demonstrated safety, and resulted in stable disease in two patients (PMID: 25895099). 25895099
EGFR act mut lung non-small cell carcinoma no benefit Ceritinib Guideline Actionable Zykadia (ceritinib) is not indicated for use in non-small cell lung cancer patients with sensitizing EGFR mutations (including exon 19 deletions and L858R) who relapsed on EGFR tyrosine kinase inhibitor therapy (NCCN.org). detail...
EGFR act mut glioblastoma multiforme sensitive BMS-754807 + Dacomitinib Preclinical - Cell culture Actionable In a preclinical study, Vizimpro (dacomitinib) and BMS-754807 worked synergistically to inhibit survival of glioblastoma cell lines harboring EGFRvIII in culture (PMID: 26561558). 26561558
EGFR act mut lung non-small cell carcinoma no benefit Alectinib Guideline Actionable Alecensa (alectinib) is not indicated for use in non-small cell lung cancer patients with sensitizing EGFR mutations (including exon 19 deletions and L858R) who relapsed on EGFR tyrosine kinase inhibitor therapy (NCCN.org). detail...
EGFR act mut lung non-small cell carcinoma sensitive Dacomitinib Phase II Actionable In a Phase II clinical trial, progression-free survival at 4 months was 95.5% in patients with EGFR-mutant non-small cell lung cancer following treatment with Vizimpro (dacomitinib), compared to 76.8% in the overall treatment population (PMID: 25456362). 25456362
EGFR act mut lung non-small cell carcinoma sensitive Dacomitinib Phase III Actionable In a Phase III (ARCHER 1050) trial, Vizimpro (dacomitinib) demonstrated superior efficacy compared to Iressa (gefitinib) as first-line therapy in non-small cell lung cancer patients harboring EGFR activating mutations (exon 19 deletion or L858R), resulting in prolonged overall survival (34.1 vs 26.8 months, HR=0.76, p=0.0438) (PMID: 29864379; NCT01774721). detail... 29864379
EGFR act mut lung non-small cell carcinoma sensitive Dacomitinib Guideline Actionable Vizimpro (dacomitinib) is included in guidelines as first-line therapy for patients with metastatic non-small cell lung cancer harboring sensitizing EGFR activating mutations (PMID: 30715168, PMID: 30285222; ESMO.org). detail... 30285222 30715168
EGFR act mut lung non-small cell carcinoma sensitive Gefitinib + Pemetrexed Phase II Actionable In a Phase II trial, Iressa (gefitinib) and pemetrexed combination therapy resulted in a median progression-free survival (PFS) of 6.7 months, an objective response rate of 22.9% (8/35), and an overall survival of 24.3 months in EGFR mutant non-small cell lung cancer patients who progressed on first-line Iressa (gefitinib), with no difference in PFS between exon 19 deletion and L858R groups (5.6 vs 7.0 months), or T790M positive and negative groups (5.9 vs 7.0 months) (PMID: 30268482). 30268482
EGFR act mut head and neck squamous cell carcinoma predicted - sensitive WSD0922 Preclinical - Pdx Actionable In a preclinical study, WSD0922 treatment resulted in tumor regression in patient-derived xenograft (PDX) models of cetuximab-resistant head and neck squamous cell carcinoma harboring EGFR activating mutations (Proceedings of the American Association for Cancer Research, Vol 60, Mar 2019, Abstract #1326). detail...
EGFR act mut lung non-small cell carcinoma predicted - sensitive MTI-31 Preclinical - Cell line xenograft Actionable In a preclinical study, MTI-31 inhibited proliferation and migration of non-small cell lung cancer cell lines harboring oncogenic EGFR mutations in culture, and inhibited tumor growth in xenograft models (PMID: 30796032). 30796032
EGFR act mut lung adenocarcinoma sensitive Bevacizumab + Erlotinib Phase II Actionable In a Phase II trial, Avastin (bevacizumab) and Tarceva (erlotinib) combination treatment resulted in a median progression-free survival of 13.2 months and a 12 month progression-free survival of 55% (60/109) in treatment-naive lung adenocarcinoma patients harboring activating EGFR mutations (exon 19 deletion or L858R) (PMID: 28408243). 28408243
EGFR act mut lung non-small cell carcinoma sensitive Rociletinib Preclinical - Cell line xenograft Actionable In a preclinical study, Rociletinib (CO-1686) inhibited tumor growth in xenograft models of human non-small cell lung cancer cell lines harboring EGFR activating mutations (PMID: 24065731). 24065731
EGFR act mut lung non-small cell carcinoma sensitive XL647 Phase II Actionable In a Phase II study, XL647 demonstrated antitumor activity and increased progression-free survival in non-small cell lung cancer patients harboring EGFR activating mutations (PMID: 22722787). 22722787
EGFR act mut Advanced Solid Tumor sensitive AP32788 Preclinical - Cell culture Actionable In a preclinical study, AP32788 inhibited growth of transformed cell lines over expressing EGFR activating mutations in culture, regardless of the presence or absence of EGFR T790M (AACR, Cancer Res: April 2016; Volume 57, Abstract #2644). detail...
EGFR act mut lung non-small cell carcinoma sensitive Erlotinib Phase II Actionable In a Phase II trial, non-small cell lung cancer patients with EGFR mutations demonstrated a median progression-free survival of 10.8 months, overall survival of 31.0 months, an overall response rate of 66.2% (137/207), and a disease control rate of 82.6% (2 complete responses; 135 partial responses, and 34 stable disease) following treatment with Tarceva (erlotinib) (PMID: 26720423). 26720423
EGFR act mut lung non-small cell carcinoma sensitive Erlotinib Guideline Actionable Tarceva (erlotinib) is included in guidelines as first-line therapy for patients with metastatic non-small cell lung cancer harboring sensitizing EGFR activating mutations (PMID: 30715168, PMID: 30285222; ESMO.org). 30285222 detail... 30715168
EGFR act mut lung non-small cell carcinoma sensitive Erlotinib Phase III Actionable In a Phase III trial, a trend toward disease free survival was observed in non-small cell lung cancer patients harboring EGFR activating mutations when treated with Tarceva (erlotinib) vs placebo in the adjuvant setting, but significance was not demonstrated due to study design (PMID: 26324372). 26324372
EGFR act mut lung non-small cell carcinoma predicted - sensitive Erlotinib + Glesatinib Phase I Actionable In a Phase I trial, Glesatinib (MGCD265) and Tarceva (erlotinib) combination treatment resulted in partial response in a non-small cell lung carcinoma patient harboring an EGFR activating mutation (J Clin Oncol 30, 2012 (suppl; abstr e13602)). detail...
EGFR act mut glioblastoma multiforme predicted - sensitive WSD0922 Preclinical - Cell line xenograft Actionable In a preclinical study, WSD0922 treatment resulted in dose-dependent inhibition of EGFRvIII phosphorylation and downstream signaling in patient-derived xenograft (PDX) models of glioblastoma multiforme, and growth inhibition in ex-vivo PDX (Proceedings of the American Association for Cancer Research, Vol 60, Mar 2019, Abstract #1326). detail...
EGFR act mut lung non-small cell carcinoma sensitive Gefitinib Phase III Actionable In a Phase III trial, adjuvant Iressa (gefitinib) treatment resulted in prolonged disease-free survival (28.7 vs 18.0 months) compared to Navelbine (vinorelbine) and Platinol (cisplatin) combination in completely resected non-small cell lung cancer patients harboring EGFR-activating mutations (J Clin Oncol 35, 2017 (suppl; abstr 8500)). detail...
EGFR act mut lung non-small cell carcinoma sensitive Gefitinib Guideline Actionable Iressa (gefitinib) is included in guidelines as first-line therapy for patients with metastatic non-small cell lung cancer harboring sensitizing EGFR activating mutations (PMID: 30715168, PMID: 30285222; ESMO.org). 30285222 30715168 detail...
EGFR act mut lung non-small cell carcinoma sensitive Gefitinib Phase III Actionable In a Phase III clinical trial, Iressa (gefitinib) treatment resulted in an objective response rate of 71.2% (94/132) and increased progression-free survival in non-small cell lung cancer patients harboring EGFR activating mutations (PMID: 19692680). 19692680
EGFR act mut lung non-small cell carcinoma sensitive Bevacizumab + Erlotinib Guideline Actionable Tarceva (erlotinib) in combination with (bevacizumab) is included in guidelines as first-line therapy for patients with metastatic non-small cell lung cancer harboring sensitizing EGFR activating mutations (PMID: 30715168, PMID: 30285222; ESMO.org). 30715168 detail... 30285222
EGFR act mut glioblastoma multiforme sensitive Gefitinib + Linsitinib Preclinical Actionable In a preclinical study, Iressa (gefitinib) and Linsitinib (OSI-906) worked synergistically to inhibit survival of glioblastoma cell lines harboring EGFRvIII in culture (PMID: 26561558). 26561558
EGFR act mut lung non-small cell carcinoma sensitive Carboplatin + Gefitinib + Pemetrexed Guideline Actionable Iressa (gefitinib) in combination with Paraplatin (carboplatin) and Alimta (pemetrexed) is included in guidelines at a first-line option for patients with metastatic non-small cell lung cancer harboring sensitizing EGFR activating mutations (PMID: 30715168, PMID: 30285222; ESMO.org). 30715168 detail... 30285222
EGFR act mut lung non-small cell carcinoma predicted - sensitive WSD0922 Preclinical - Cell line xenograft Actionable In a preclinical study, WSD0922 treatment prolonged survival in cell line xenograft models of intracranial metastasis of non-small cell lung cancer harboring EGFR activating mutations (Proceedings of the American Association for Cancer Research, Vol 60, Mar 2019, Abstract #1326). detail...
EGFR act mut lung squamous cell carcinoma predicted - sensitive WSD0922 Preclinical - Pdx Actionable In a preclinical study, WSD0922 treatment resulted in tumor regression in patient-derived xenograft (PDX) models of squamous lung cancer harboring EGFR activating mutations (Proceedings of the American Association for Cancer Research, Vol 60, Mar 2019, Abstract #1326). detail...
EGFR act mut lung non-small cell carcinoma no benefit Brigatinib Guideline Actionable Alunbrig (brigatinib) is not indicated for use in non-small cell lung cancer patients with sensitizing EGFR mutations (including exon 19 deletions and L858R) who relapsed on EGFR tyrosine kinase inhibitor therapy (NCCN.org). detail...
EGFR C797S EGFR act mut Advanced Solid Tumor resistant Osimertinib Preclinical - Cell culture Actionable In a preclinical study, overexpression of EGFR C797S in addition to other EGFR activating mutations including L858R, T790M, and exon 19 deletion (L747_P753delinsS) conferred resistance to Tagrisso (osimertinib) in transformed cells in culture (PMID: 29285266). 29285266
EGFR C797S EGFR act mut Advanced Solid Tumor resistant Afatinib Preclinical - Cell culture Actionable In a preclinical study, overexpression of EGFR C797S in addition to other EGFR activating mutations including L858R, T790M, and exon 19 deletion (L747_P753delinsS) conferred resistance to Gilotrif (afatinib) in transformed cells in culture (PMID: 29285266). 29285266
EGFR C797S EGFR act mut Advanced Solid Tumor resistant Nazartinib Preclinical - Cell culture Actionable In a preclinical study, overexpression of EGFR C797S in addition to other EGFR activating mutations including L858R, T790M, and exon 19 deletion (L747_P753delinsS) conferred resistance to Nazartinib (EGF816) in transformed cells in culture (PMID: 29285266). 29285266
EGFR C797S EGFR act mut lung non-small cell carcinoma resistant Naquotinib Phase I Actionable In a Phase I trial, three non-small cell lung carcinoma patients initially harboring EGFR T790M and/or an EGFR activating mutation demonstrated a partial response to ASP8273 treatment, but later progressed, demonstrating in cell-free DNA, a reemergence of EGFR T790M and/or the EGFR activating mutation and EGFR C797S (PMID: 28954786; NCT02113813). 28954786
EGFR C797S EGFR act mut Advanced Solid Tumor resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, overexpression of EGFR C797S in addition to other EGFR activating mutations including L858R, T790M, and exon 19 deletion (L747_P753delinsS) conferred resistance to Tarceva (erlotinib) in transformed cells in culture (PMID: 29285266). 29285266
EGFR act mut EGFR amp glioblastoma multiforme predicted - sensitive Depatuxizumab mafodotin + Radiotherapy + Temozolomide Preclinical - Cell line xenograft Actionable In a preclinical study, ABT-414 in combination with Temodar (temozolomide) and radiotherapy inhibited tumor growth and resulted in tumor growth delay in a glioblastoma multiforme cell line xenograft model harboring amplified EGFR vIII (exon 2-7 deletion), with increased efficacy compared to the combination of Temodar (temozolomide) and radiotherapy (PMID: 26846818). 26846818
EGFR act mut EGFR amp glioblastoma multiforme predicted - sensitive Depatuxizumab mafodotin Preclinical - Cell line xenograft Actionable In a preclinical study, ABT-414 induced cytoxicity in a glioblastoma cell line harboring amplified EGFR vIII (exon 2-7 deletion) in culture, and induced complete tumor regression in cell line xenograft models of glioblastoma harboring amplified EGFR vIII (PMID: 26846818). 26846818
EGFR act mut MET amp lung cancer sensitive SYM015 Preclinical - Pdx Actionable In a preclinical study, SYM015 treatment resulted in tumor growth inhibition in patient-derived xenograft (PDX) models of MET-amplified lung cancer harboring EGFR activating mutations (PMID: 28679766). 28679766
EGFR T790M EGFR act mut PIK3CA E545K lung non-small cell carcinoma predicted - resistant Rociletinib Clinical Study - Cohort Actionable In a retrospective analysis of a Phase I and a Phase II trial, PIK3CA activating mutations were identified at disease progression in 12% (5/43) of patients with non-small cell lung cancer harboring both EGFR T790M and another EGFR activating mutation (exon 19 deletion, n=3; L858R, n=2) treated with Rociletinib (CO-1686), PIK3CA E545K was identified in 4 of the 5 patients (PMID: 27283993; NCT01526928, NCT02147990). 27283993
EGFR T790M EGFR act mut EGFR amp lung non-small cell carcinoma predicted - resistant Rociletinib Clinical Study - Cohort Actionable In a retrospective analysis of a Phase I and a Phase II trial, EGFR amplification was identified at disease progression in 9% (4/43) of patients with non-small cell lung cancer harboring both EGFR T790M and another EGFR activating mutation (exon 19 deletion, 70%; L858R, 28%) treated with Rociletinib (CO-1686), conversely, preexisting MET, ERBB2 (HER2), or EGFR amplification were more common in patients with primary resistance to Rociletinib (CO-1686) (PMID: 27283993; NCT01526928, NCT02147990). 27283993
EGFR act mut EGFR C797S EGFR T790M lung non-small cell carcinoma resistant Naquotinib Phase I Actionable In a Phase I trial, three non-small cell lung carcinoma patients initially harboring EGFR T790M and/or an EGFR activating mutation demonstrated a partial response to ASP8273 treatment, but later progressed, demonstrating in cell-free DNA, a reemergence of EGFR T790M and/or the EGFR activating mutation and EGFR C797S (PMID: 28954786; NCT02113813). 28954786
EGFR act mut EGFR T790M MET amp lung non-small cell carcinoma predicted - resistant Rociletinib Clinical Study - Cohort Actionable In a retrospective analysis of a Phase I and a Phase II trial, MET amplification was identified at disease progression in 26% (11/43) of patients with non-small cell lung cancer harboring both EGFR T790M and another EGFR activating mutation (exon 19 deletion, 70%; L858R, 28%) treated with Rociletinib (CO-1686), conversely, preexisting MET, ERBB2 (HER2), or EGFR amplification were more common in patients with primary resistance to Rociletinib (CO-1686) (PMID: 27283993; NCT01526928, NCT02147990). 27283993
EGFR T790M EGFR act mut ERBB2 amp lung non-small cell carcinoma predicted - resistant Rociletinib Clinical Study - Cohort Actionable In a retrospective analysis of a Phase I and a Phase II trial, ERBB2 (HER2) amplification was identified at disease progression in 9% (4/43) of patients with non-small cell lung cancer harboring both EGFR T790M and another EGFR activating mutation (exon 19 deletion, 70%; L858R, 28%) treated with Rociletinib (CO-1686), conversely, preexisting MET, ERBB2 (HER2), or EGFR amplification were more common in patients with primary resistance to Rociletinib (CO-1686) (PMID: 27283993; NCT01526928, NCT02147990). 27283993
EGFR T790M EGFR act mut PIK3CA E542K lung non-small cell carcinoma predicted - resistant Rociletinib Clinical Study - Cohort Actionable In a retrospective analysis of a Phase I and a Phase II trial, PIK3CA activating mutations were identified at disease progression in 12% (5/43) of patients with non-small cell lung cancer harboring both EGFR T790M and another EGFR activating mutation (exon 19 deletion, n=3; L858R, n=2) treated with Rociletinib (CO-1686), PIK3CA E542K was identified in 3 of the 5 patients (PMID: 27283993; NCT01526928, NCT02147990). 27283993
EGFR amp EGFR wild-type EGFR act mut glioblastoma multiforme predicted - sensitive Depatuxizumab mafodotin Preclinical - Pdx Actionable In a preclinical study, ABT-414 induced tumor regression in a patient-derived xenograft model of glioblastoma multiforme harboring amplified wild-type EGFR and EGFR vIII (exon 2-7 deletion) (PMID: 26846818). 26846818
EGFR amp EGFR act mut PTEN R308C glioblastoma multiforme sensitive BMS-754807 + Dacomitinib Preclinical - Cell culture Actionable In a preclinical study, Vizimpro (dacomitinib) and BMS-754807 worked synergistically to inhibit survival of glioblastoma cell lines harboring EGFR amplification, EGFRvIII, and PTEN R308C in culture (PMID: 26561558). 26561558
EGFR amp EGFR act mut PTEN R308C glioblastoma multiforme sensitive Gefitinib + Linsitinib Preclinical Actionable In a preclinical study, Iressa (gefitinib) and Linsitinib (OSI-906) worked synergistically to inhibit survival of glioblastoma cell lines harboring EGFR amplification, EGFRvIII, and PTEN R308C in culture (PMID: 26561558). 26561558
EGFR act mut EGFR A289T PTEN I253N PTEN N69D glioblastoma multiforme sensitive BMS-754807 + Dacomitinib Preclinical - Cell culture Actionable In a preclinical study, Vizimpro (dacomitinib) and BMS-754807 worked synergistically to inhibit survival of glioblastoma cell lines harboring EGFR (A289T, EGFRvIII) and PTEN (N69D, I253N) mutations in culture (PMID: 26561558). 26561558
EGFR act mut EGFR A289T PTEN I253N PTEN N69D glioblastoma multiforme sensitive Gefitinib + Linsitinib Preclinical Actionable In a preclinical study, Iressa (gefitinib) and Linsitinib (OSI-906) worked synergistically to inhibit survival of glioblastoma cell lines harboring mutations in EGFR (EGFRvIII, A289T) and PTEN (I253N, N69D) in culture (PMID: 26561558). 26561558
EGFR act mut EGFR T790M lung non-small cell carcinoma predicted - sensitive MTI-31 Preclinical - Cell line xenograft Actionable In a preclinical study, MTI-31 inhibited proliferation and migration and increased PD-L1 degradation in a non-small cell lung cancer cell line harboring an oncogenic EGFR mutation and secondary EGFR T790M mutation in culture, and inhibited tumor growth in xenograft models (PMID: 30796032). 30796032
EGFR act mut EGFR T790M lung non-small cell carcinoma sensitive Naquotinib Phase I Actionable In a Phase I trial, treatment with ASP8273 resulted in a partial response in 41% (19/46) of non-small cell lung carcinoma patients co-harboring EGFR T790M and an EGFR activating mutation, demonstrating almost undetectable levels of the mutations in cell-free DNA (PMID: 28954786; NCT02113813). 28954786
EGFR act mut EGFR T790M lung adenocarcinoma sensitive Bevacizumab + Erlotinib Phase II Actionable In a Phase II trial, Avastin (bevacizumab) and Tarceva (erlotinib) combination treatment resulted in a median progression-free survival of 16.0 months and a 12 month progression-free survival of 68% (25/37) in treatment-naive lung adenocarcinoma patients harboring activating EGFR mutations (exon 19 deletion or L858R) and EGFR T790M (PMID: 28408243). 28408243
EGFR act mut EGFR T790M lung non-small cell carcinoma no benefit Erlotinib + Luminespib Phase Ib/II Actionable In a Phase Ib/II clinical trial, the combination of Luminespib (AUY922) and Tarceva (erlotinib) demonstrated limited clinical benefit in patients with EGFR-mutant non-small cell carcinoma with acquired resistance to EGFR tyrosine kinase inhibitors, including patients with EGFR T790M, with 16% (4/25) patients achieving partial response (PMID: 25870087). 25870087
EGFR act mut EGFR T790M lung non-small cell carcinoma predicted - resistant Gefitinib Phase II Actionable In a Phase II trial, EGFR T790M was identified at disease progression in 54% (19/35) of non-small cell lung cancer patients harboring sensitizing EGFR mutations (15 exon 19 deletion, 20 L858R) who received Iressa (gefitinib) as first-line treatment (PMID: 30268482). 30268482
EGFR E746_T751delinsV Advanced Solid Tumor resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR E746_T751delinsV were resistant to treatment with Erbitux (cetuximab) in culture (PMID: 29141884). 29141884
EGFR E746_T751delinsV Advanced Solid Tumor sensitive Gefitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR E746_T751delinsV were sensitive to treatment with Iressa (gefitinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR E746_T751delinsV Advanced Solid Tumor sensitive Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR E746_T751delinsV were sensitive to treatment with Tarceva (erlotinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR E746_T751delinsV Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR E746_T751delinsV were sensitive to treatment with Gilotrif (afatinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR E746_T751delinsV Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR E746_T751delinsV were sensitive to treatment with Tagrisso (osimertinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR exon 19 ins lung non-small cell carcinoma sensitive Erlotinib Guideline Actionable Tarceva (erlotinib) is included in guidelines as first-line therapy for patients with advanced or metastatic non-small cell lung cancer harboring sensitizing EGFR mutations, such as exon 19 insertions (NCCN.org). detail...
EGFR exon 19 ins lung non-small cell carcinoma sensitive Gefitinib Guideline Actionable Iressa (gefitinib) is included in guidelines as first-line therapy for patients with advanced or metastatic non-small cell lung cancer harboring sensitizing EGFR mutations, such as exon 19 insertions (NCCN.org). detail...
EGFR exon 19 ins lung non-small cell carcinoma sensitive Dacomitinib Guideline Actionable Vizimpro (dacomitinib) is included in guidelines as first-line therapy for patients with advanced or metastatic non-small cell lung cancer harboring sensitizing EGFR mutations, such as exon 19 insertions (NCCN.org). detail...
EGFR exon 19 ins lung non-small cell carcinoma sensitive Osimertinib Guideline Actionable Tagrisso (osimertinib) is included in guidelines as preferred first-line or as subsequent therapy for patients with advanced or metastatic non-small cell lung cancer harboring sensitizing EGFR mutations, such as exon 19 insertions (NCCN.org). detail...
EGFR exon 19 ins lung non-small cell carcinoma sensitive Afatinib Guideline Actionable Gilotrif (afatinib) is included in guidelines as first-line therapy for patients with advanced or metastatic non-small cell lung cancer harboring sensitizing EGFR mutations, such as exon 19 insertions (NCCN.org). detail...
EGFR L858R EGFR T854A Advanced Solid Tumor predicted - resistant Gefitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EGFR L858R and EGFR T854A were mildly resistant to Iressa (gefitinib) in culture (PMID: 29702287). 29702287
EGFR L858R EGFR T854A Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EGFR L858R and EGFR T854A were sensitive to treatment with Gilotrif (afatinib) in culture, demonstrating decreased cell growth (PMID: 29702287). 29702287
EGFR L858R EGFR T854A Advanced Solid Tumor predicted - sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EGFR L858R and EGFR T854A were moderately sensitive to Alunbrig (brigatinib) in culture, demonstrating reduced cell growth (PMID: 29702287). 29702287
EGFR L858R EGFR T854A Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EGFR L858R and EGFR T854A were sensitive to treatment with Tagrisso (osimertinib) in culture, demonstrating decreased cell growth (PMID: 29702287). 29702287
EGFR L858R EGFR T854A Advanced Solid Tumor decreased response Erlotinib Preclinical Actionable In a preclinical study, expression of EGFR T854A decreased sensitivity of transformed cells expressing EGFR L858R to Tarceva (erlotinib) in culture (PMID: 19010870). 19010870
EGFR L858R EGFR T854A lung adenocarcinoma resistant Erlotinib Case Reports/Case Series Actionable In a clinical case study, EGFR T854A was identified as an acquired mutation conferring resistance to Iressa (gefitinib) in a patient with lung adenocarcinoma harboring EGFR L858R, which was supported by decreased response to Iressa (gefitinib) in cells expressing EGFR L858R and T854A in culture (PMID: 19010870). 19010870
EGFR C797S EGFR L858R EGFR T854A Advanced Solid Tumor predicted - resistant Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EGFR C797S, EGFR L858R, and EGFR T854A demonstrated some resistance to Gilotrif (afatinib) in culture (PMID: 29702287). 29702287
EGFR C797S EGFR L858R EGFR T854A Advanced Solid Tumor resistant Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EGFR C797S, EGFR L858R, and EGFR T854A demonstrated resistance to treatment with Tagrisso (osimertinib) (PMID: 29702287). 29702287
EGFR C797S EGFR L858R EGFR T854A Advanced Solid Tumor predicted - resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EGFR C797S, EGFR L858R, and EGFR T854A demonstrated some resistance to Alunbrig (brigatinib) in culture (PMID: 29702287). 29702287
EGFR C797S EGFR L858R EGFR T854A Advanced Solid Tumor predicted - resistant Gefitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EGFR C797S, EGFR L858R, and EGFR T854A demonstrated some resistance to Iressa (gefitinib) in culture (PMID: 29702287). 29702287
EGFR T854A Advanced Solid Tumor resistant Rociletinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR T854A were resistant to treatment with Rociletinib (CO-1686) in culture (PMID: 29141884). 29141884
EGFR T854A Advanced Solid Tumor resistant Gefitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR T854A were resistant to treatment with Iressa (gefitinib) in culture (PMID: 29141884). 29141884
EGFR T854A Advanced Solid Tumor resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR T854A were resistant to treatment with Tarceva (erlotinib) in culture (PMID: 29141884). 29141884
EGFR T854A Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR T854A were sensitive to treatment with Tagrisso (osimertinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR T854A Advanced Solid Tumor resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR T854A were resistant to treatment with Erbitux (cetuximab) in culture (PMID: 29141884). 29141884
EGFR C797S EGFR exon 19 del EGFR T854A Advanced Solid Tumor resistant Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EGFR C797S, EGFR exon 19 del, and EGFR T854A were resistant to treatment with Tagrisso (osimertinib) (PMID: 29702287). 29702287
EGFR C797S EGFR exon 19 del EGFR T854A Advanced Solid Tumor decreased response Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EGFR C797S, EGFR exon 19 del, and EGFR T854A demonstrated a decreased response to Gilotrif (afatinib) in culture when compared to Alunbrig (brigatinib) (PMID: 29702287). 29702287
EGFR C797S EGFR exon 19 del EGFR T854A Advanced Solid Tumor decreased response Gefitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EGFR C797S, EGFR exon 19 del, and EGFR T854A demonstrated a decreased response to Iressa (gefitinib) in culture when compared to Alunbrig (brigatinib) (PMID: 29702287). 29702287
EGFR C797S EGFR exon 19 del EGFR T854A Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EGFR C797S, EGFR exon19 del, and EGFR T854A were sensitive to treatment with Alunbrig (brigatinib) in culture, demonstrating reduced cell growth (PMID: 29702287). 29702287
EGFR exon 19 del EGFR T854A Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EGFR exon 19 del and EGFR T854A were sensitive to treatment with Tagrisso (osimertinib), demonstrating reduced cell growth (PMID: 29702287). 29702287
EGFR exon 19 del EGFR T854A Advanced Solid Tumor predicted - resistant Gefitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR exon 19 del and EGFR T854A were moderately resistant to Iressa (gefitinib) in culture (PMID: 29702287). 29702287
EGFR exon 19 del EGFR T854A Advanced Solid Tumor predicted - sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR exon 19 del and EGFR T854A were moderately resistant to Alunbrig (brigatinib) in culture (PMID: 29702287). 29702287
EGFR exon 19 del EGFR T854A Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EGFR exon 19 del and EGFR T854A were sensitive to treatment with Gilotrif (afatinib), demonstrating reduced cell growth (PMID: 29702287). 29702287
EGFR E709K EGFR L858R Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, treatment with Tagrisso (osimertinib) resulted in decreased growth of transformed cells expressing EGFR E709K and EGFR L858R in cis and trans in culture (PMID: 29141884). 29141884
EGFR E709K EGFR L858R Advanced Solid Tumor resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR E709K and EGFR L858R in cis and trans were resistant to Erbitux (cetuximab) in culture (PMID: 29141884). 29141884
EGFR E709K EGFR L858R Advanced Solid Tumor sensitive Erlotinib Preclinical - Cell culture Actionable In a preclinical study, treatment with Tarceva (erlotinib) resulted in decreased growth of transformed cells expressing EGFR E709K and EGFR L858R in cis and trans in culture (PMID: 29141884). 29141884
EGFR E709K EGFR L858R Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, treatment with Gilotrif (afatinib) resulted in decreased growth of transformed cells expressing EGFR E709K and EGFR L858R in cis and trans in culture (PMID: 29141884). 29141884
EGFR E709K Advanced Solid Tumor sensitive Afatinib Preclinical Actionable In a preclinical study, transformed cells expressing EGFR E709K demonstrated increased sensitivity to second-generation EGFR inhibitors including Gilotrif (afatinib) in culture, when compared to first and third-generation inhibitors (PMID: 26206867). 26206867
EGFR E709K Advanced Solid Tumor decreased response Gefitinib Preclinical Actionable In a preclinical study, transformed cells expressing EGFR E709K demonstrated decreased sensitivity to first-generation EGFR inhibitors including Iressa (gefitinib) in culture, when compared to second-generation inhibitors (PMID: 26206867). 26206867
EGFR E709K Advanced Solid Tumor sensitive Neratinib Preclinical Actionable In a preclinical study, transformed cells expressing EGFR E709K demonstrated increased sensitivity to second-generation EGFR inhibitors including Nerlynx (neratinib) in culture, when compared to first and third-generation inhibitors (PMID: 26206867). 26206867
EGFR E709K Advanced Solid Tumor decreased response Osimertinib Preclinical Actionable In a preclinical study, transformed cells expressing EGFR E709K demonstrated decreased sensitivity to third-generation EGFR inhibitors including Tagrisso (AZD9291) in culture, when compared to second-generation inhibitors (PMID: 26206867). 26206867
EGFR E709K Advanced Solid Tumor sensitive Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR E709K were sensitive to treatment with Erbitux (cetuximab) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR E709K Advanced Solid Tumor sensitive Dacomitinib Preclinical Actionable In a preclinical study, transformed cells expressing EGFR E709K demonstrated increased sensitivity to second-generation EGFR inhibitors including Vizimpro (dacomitinib) in culture, when compared to first and third-generation inhibitors (PMID: 26206867). 26206867
EGFR E709K Advanced Solid Tumor decreased response Rociletinib Preclinical Actionable In a preclinical study, transformed cells expressing EGFR E709K demonstrated decreased sensitivity to third-generation EGFR inhibitors including Rociletinib (CO-1686) in culture, when compared to second-generation inhibitors (PMID: 26206867). 26206867
EGFR E709K Advanced Solid Tumor decreased response Erlotinib Preclinical Actionable In a preclinical study, transformed cells expressing EGFR E709K demonstrated decreased sensitivity to first-generation EGFR inhibitors including Tarceva (erlotinib) in culture, when compared to second-generation inhibitors (PMID: 26206867). 26206867
EGFR G874S Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR G874S were sensitive to treatment with Gilotrif (afatinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR G874S Advanced Solid Tumor sensitive Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR G874S were sensitive to treatment with Tarceva (erlotinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR G874S Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR G874S were sensitive to treatment with Tagrisso (osimertinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR I941R EGFR L858R EGFR T790M Advanced Solid Tumor sensitive EAI045 Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing EGFR that harbors concomitant L858R, T790M and I941R mutations demonstrated increased sensitivity to EAI045 induced growth inhibition in culture (PMID: 27251290). 27251290
EGFR T790M EGFR L858R EGFR A871G TP53 R248W RB1 K844S lung non-small cell carcinoma predicted - sensitive Erlotinib Case Reports/Case Series Actionable In a clinical case study, Tarceva (erlotinib) treatment resulted in gradual tumor reduction and improved quality of life lasted for 1.5 years in a patient with metastatic non-small cell lung cancer harboring EGFR T790M, L858R, and A871G, TP53 R248W, and RB1 K844S (PMID: 31045832). 31045832
EGFR A871G Advanced Solid Tumor sensitive Gefitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A871G were sensitive to treatment with Iressa (gefitinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR A871G Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A871G were sensitive to treatment with Tagrisso (osimertinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR A871G Advanced Solid Tumor resistant Rociletinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A871G were resistant to treatment with Rociletinib (CO-1686) in culture (PMID: 29141884). 29141884
EGFR A871G Advanced Solid Tumor sensitive Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A871G were sensitive to treatment with Tarceva (erlotinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR A871G Advanced Solid Tumor resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A871G were resistant to treatment with Erbitux (cetuximab) in culture (PMID: 29141884). 29141884
EGFR A871G Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A871G were sensitive to treatment with Gilotrif (afatinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR R776C Advanced Solid Tumor resistant Rociletinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR R776C were resistant to treatment with Rociletinib (CO-1686) in culture (PMID: 29141884). 29141884
EGFR R776C Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR R776C were sensitive to treatment with Tagrisso (osimertinib) in culture (PMID: 29141884). 29141884
EGFR R776C Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR R776C were sensitive to treatment with Gilotrif (afatinib) in culture (PMID: 29141884). 29141884
EGFR R776C Advanced Solid Tumor sensitive Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR R776C were sensitive to treatment with Tarceva (erlotinib) in culture (PMID: 29141884). 29141884
EGFR T34_A289del neuroblastoma resistant Etoposide Preclinical - Cell culture Actionable In a preclinical study, neuroblastoma cells over expressing EGFR T34_A289del were resistant to Eposin (etoposide) in culture (PMID: 27216155). 27216155
EGFR T34_A289del neuroblastoma sensitive Erlotinib Preclinical - Cell culture Actionable In a preclinical study, Tarceva (erlotinib) inhibited Egfr phosphorylation and cell proliferation in neuroblastoma cells over expressing EGFR T34_A289del in culture (PMID: 27216155). 27216155
EGFR T34_A289del Advanced Solid Tumor decreased response Cetuximab Preclinical - Cell culture Actionable In a preclinical study, Erbitux (cetuximab) did not efficiently inhibit Egfr phosphorylation in transformed cells over expressing T34_A289del in culture (PMID: 27216155). 27216155
EGFR T34_A289del Advanced Solid Tumor sensitive Erlotinib Preclinical - Cell culture Actionable In a preclinical study, Tarceva (erlotinib) inhibited Egfr phosphorylation and cell proliferation in transformed cells over expressing EGFR T34_A289del in culture (PMID: 27216155). 27216155
EGFR E746_S752del EGFR T790M EGFR P794L lung non-small cell carcinoma predicted - sensitive Afatinib Case Reports/Case Series Actionable In a clinical case study, Gilotrif (afatinib) treatment resulted in rapid clinical response in a patient with non-small cell lung carcinoma harboring an EGFR exon 19 deletion (E746_S752del), EGFR T790M and EGFR P794L (PMID: 29704676). 29704676
EGFR E746_S752del EGFR T790M EGFR P794L lung non-small cell carcinoma predicted - resistant Osimertinib Case Reports/Case Series Actionable In a clinical case study, Tagrisso (osimertinib) treatment resulted in initial response in a patient with non-small cell lung carcinoma harboring an EGFR exon 19 deletion (E746_S752del) and T790M, however, the disease progressed 20 months after treatment started, and EGFR P794L was identified by liquid biopsy at the time of progression (PMID: 29704676). 29704676
EGFR T790M EGFR G796R EGFR L858R Advanced Solid Tumor resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, Erbitux (cetuximab) did not inhibit proliferation of transformed cells expressing EGFR L858R and T790M in cis with EGFR G796R in culture (PMID: 29857056). 29857056
EGFR T790M EGFR G796R EGFR L858R Advanced Solid Tumor resistant Cetuximab + EAI045 Preclinical - Cell culture Actionable In a preclinical study, combination of EAI045 and Erbitux (cetuximab) did not inhibit proliferation of transformed cells expressing EGFR L858R and T790M in cis with EGFR G796R in culture (PMID: 29857056). 29857056
EGFR T790M EGFR G796R EGFR L858R Advanced Solid Tumor resistant EAI045 Preclinical - Cell culture Actionable In a preclinical study, EAI045 did not inhibit proliferation of transformed cells expressing EGFR L858R and T790M in cis with EGFR G796R in culture (PMID: 29857056). 29857056
EGFR T790M EGFR G796R EGFR L858R Advanced Solid Tumor resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, Tarceva (erlotinib) did not inhibit proliferation of transformed cells expressing EGFR L858R and T790M in cis with EGFR L792HG796R in culture (PMID: 29857056). 29857056
EGFR T790M EGFR G796R EGFR L858R Advanced Solid Tumor resistant Afatinib Preclinical - Cell culture Actionable In a preclinical study, Gilotrif (afatinib) did not inhibit proliferation of transformed cells expressing EGFR L858R and T790M in cis with EGFR G796R in culture (PMID: 29857056). 29857056
EGFR T790M EGFR G796R EGFR L858R Advanced Solid Tumor resistant Osimertinib Preclinical - Cell culture Actionable In a preclinical study, Tagrisso (osimertinib) did not inhibit Egfr phosphorylation and proliferation of transformed cells expressing EGFR L858R and T790M in cis with EGFR G796R in culture (PMID: 29857056). 29857056
EGFR T790M EGFR G796R lung adenocarcinoma predicted - resistant Osimertinib Case Reports/Case Series Actionable In a retrospective analysis, EGFR G796R was identified in 0.59% (2/340) of lung adenocarcinoma patients receiving Tagrisso (osimertinib), and 1 of the 2 patients also had EGFR T790M in cis, consistent with cell culture study and structural modeling that supports a role of EGFR G796R in cis with T790M in conferring resistance to Tagrisso (osimertinib) (PMID: 29857056). 29857056
EGFR amp EGFR E746_A750del lung adenocarcinoma sensitive Depatuxizumab mafodotin Preclinical - Cell line xenograft Actionable In a preclinical study, ABT-414 demonstrated cytotoxicity against a lung adenocarcinoma cell line that harbored EGFR amplification and EGFR E746_A750del in culture and induced tumor regression in cell line xenograft models (PMID: 26846818). 26846818
EGFR amp esophagus squamous cell carcinoma resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, esophagus squamous cell carcinoma cells harboring EGFR amplification demonstrated resistance to Erbitux (cetuximab) in a cell viability assay (PMID: 27207775). 27207775
EGFR amp gastric adenocarcinoma predicted - sensitive ABT-806 Clinical Study - Cohort Actionable In a clinical study, anti-Egfr antibody therapies including Erbitux (cetuximab) and ABT-806, alone or in combination with chemotherapy, resulted in an objective response in 57% (4/7, 3 complete response, 1 partial response), and disease control in 43% (3/7) of patients with EGFR amplified gastric and esophagogastric junction adenocarcinoma with a mean circulating tumor DNA copy number of 2.5 in non-responders vs 33.9 in responders (p=0.049) (PMID: 29449271). 29449271
EGFR amp gastroesophageal junction adenocarcinoma predicted - sensitive ABT-806 Clinical Study - Cohort Actionable In a clinical study, anti-Egfr antibody therapies including Erbitux (cetuximab) and ABT-806, alone or in combination with chemotherapy, resulted in an objective response in 57% (4/7, 3 complete response, 1 partial response), and disease control in 43% (3/7) of patients with EGFR amplified gastric and esophagogastric junction adenocarcinoma with a mean circulating tumor DNA copy number of 2.5 in non-responders vs 33.9 in responders (p=0.049) (PMID: 29449271). 29449271
EGFR amp gastric adenocarcinoma predicted - sensitive Cetuximab Clinical Study - Cohort Actionable In a clinical study, anti-Egfr antibody therapies including Erbitux (cetuximab) and ABT-806, alone or in combination with chemotherapy, resulted in an objective response in 57% (4/7, 3 complete response, 1 partial response), and disease control in 43% (3/7) of patients with EGFR amplified gastric and esophagogastric junction adenocarcinoma with a mean circulating tumor DNA copy number of 2.5 in non-responders vs 33.9 in responders (p=0.049) (PMID: 29449271). 29449271
EGFR amp glioblastoma multiforme sensitive Depatuxizumab mafodotin Phase I Actionable In a Phase I trial, treatment with Depatuxizumab mafodotin (ABT-414) resulted in an overall response rate of 6.7% (3/59; 1 complete response and 2 partial responses), stable disease in 41% (27/66), and a progression-free survival rate of 28.8% (95% CI 18.5, 39.9%) at 6 months in patients with EGFR-amplified recurrent glioblastoma (PMID: 29075855; NCT01800695). detail... 29075855
EGFR amp triple-receptor negative breast cancer sensitive Gefitinib + PF-431396 Preclinical - Cell culture Actionable In a preclinical study, the combination of Iressa (gefitinib) and PF-431396 resulted in a synergistic effect in a triple-receptor negative breast cancer cell line harboring EGFR amplification, demonstrating a decrease in colony formation in culture (PMID: 27793840). 27793840
EGFR amp esophagus adenocarcinoma predicted - resistant AMG 337 Case Reports/Case Series Actionable In a clinical case study, a patient with esophageal adenocarcinoma progressed on AMG 337 therapy upon outgrowth of EGFR amplified tumor cells (PMID: 26432108). 26432108
EGFR amp gastroesophageal junction adenocarcinoma predicted - sensitive Cetuximab Clinical Study - Cohort Actionable In a clinical study, anti-Egfr antibody therapies including Erbitux (cetuximab) and ABT-806, alone or in combination with chemotherapy, resulted in an objective response in 57% (4/7, 3 complete response, 1 partial response), and disease control in 43% (3/7) of patients with EGFR amplified gastric and esophagogastric junction adenocarcinoma with a mean circulating tumor DNA copy number of 2.5 in non-responders vs 33.9 in responders (p=0.049) (PMID: 29449271). 29449271
EGFR amp glioblastoma multiforme no benefit Temozolomide + Vandetanib Phase II Actionable In a Phase II trial, Caprelsa (vandetinib), in combination with radiation therapy and Temodar (temozolomide), demonstrated no difference in PFS and OS in glioblastoma patients harboring EGFR amplification versus glioblastoma patients without EGFR amplification (PMID: 25910950). 25910950
EGFR amp penile cancer sensitive ABT-806 Phase I Actionable In a Phase I trial, ABT-806 treatment resulted in stable disease for more than 2.5 years in a penile cancer patient harboring EGFR amplification (PMID: 25895099). 25895099
EGFR amp triple-receptor negative breast cancer sensitive Depatuxizumab mafodotin Phase Ib/II Actionable In a Phase I/II trial, Depatuxizumab mafodotin (ABT-414) treatment resulted in partial response in a patient with EGFR amplified triple-receptor negative breast cancer (PMID: 29533458; NCT01741727). 29533458
EGFR amp triple-receptor negative breast cancer sensitive Depatuxizumab mafodotin Preclinical Actionable In a preclinical study, ABT-414 demonstrated cytotoxicity against a EGFR-amplified triple-negative breast cancer cell line in culture (PMID: 26846818). 26846818
EGFR amp Advanced Solid Tumor sensitive Depatuxizumab mafodotin Phase Ib/II Actionable In a Phase I/II trial, Depatuxizumab mafodotin (ABT-414) treatment resulted in partial response in 1.8% (1/56) and stable disease in 23% (13/56) of patients with advanced solid tumor harboring EGFR amplification, overexpression, or mutated EGFR variant III (PMID: 29533458; NCT01741727). 29533458
EGFR amp Advanced Solid Tumor sensitive Depatuxizumab mafodotin Phase I Actionable In a Phase I trial, ABT-414 displayed safety and preliminary efficacy in advanced solid tumor patients with EGFR amplification (J Clin Oncol 33, 2015 (suppl; abstr 2510)). detail...
EGFR amp Advanced Solid Tumor predicted - sensitive MM-151 Preclinical Actionable In a preclinical study, MM-151 antagonized EGFR activity and inhibited proliferation in several tumor cell lines in culture (PMID: 25911688). 25911688
EGFR amp urinary bladder cancer no benefit Afatinib Phase II Actionable In a Phase II clinical trial, three urothelial carcinoma patients with EGFR amplification in the absence of other ERBB family member alterations, received no benefit from Gilotrif (afatinib) therapy (PMID: 27044931). 27044931
EGFR amp glioblastoma multiforme sensitive Dacomitinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Vizimpro (dacomitinib) inhibited Egfr signaling and survival of patient-derived EGFR amplified glioblastoma cells in culture and in intracranial xenograft models (PMID: 25939761). 25939761
EGFR amp head and neck squamous cell carcinoma resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, head and neck squamous cell carcinoma cells harboring EGFR amplification demonstrated resistance to Erbitux (cetuximab) in a cell viability assay (PMID: 27207775). 27207775
EGFR amp esophagus squamous cell carcinoma resistant Afatinib Preclinical - Cell culture Actionable In a preclinical study, esophagus squamous cell carcinoma cells harboring EGFR amplification demonstrated resistance to Gilotrif (afatinib) in a cell viability assay (PMID: 27207775). 27207775
EGFR amp head and neck cancer sensitive unspecified EGFR antibody + unspecified ERBB3 antibody + unspecified IGF-1R antibody Preclinical - Cell culture Actionable In a preclinical study, combination of an unspecified EGFR antibody, an unspecified Erbb3 (Her3) antibody, and an unspecified Igf-1r antibody resulted in potent inhibition of survival in Egfr amplified head and neck cancer cells that developed Erbitux (cetuximab) resistance in culture (PMID: 27196767). 27196767
EGFR amp triple-receptor negative breast cancer sensitive Gefitinib + PF-573228 Preclinical - Cell culture Actionable In a preclinical study, the combination of Iressa (gefitinib) and PF-573228 resulted in a synergistic effect in a triple-receptor negative breast cancer cell line harboring EGFR amplification, demonstrating decreased colony formation in culture (PMID: 27793840). 27793840
EGFR amp head and neck squamous cell carcinoma sensitive Afatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Gilotrif (afatinib) inhibited growth of head and neck squamous cell carcinoma (HNSCC) cell lines in culture, and inhibited tumor growth in HNSCC cell line xenograft models, with highest efficacy against EGFR-amplified cell lines (PMID: 25559287). 25559287
EGFR amp lung non-small cell carcinoma sensitive Ganetespib Preclinical - Cell culture Actionable In a preclinical study, Ganetespib inhibited growth of a non-small cell lung cancer cell line with EGFR amplification and overexpression in culture (PMID: 25077897). 25077897
EGFR amp gastrointestinal system cancer sensitive Cetuximab Preclinical - Pdx Actionable In preclinical studies, Erbitux (cetuximab) promoted tumor growth inhibition in several patient-derived xenograft models of gastric cancers with EGFR amplification (PMID: 24141978). 24141978
EGFR amp head and neck cancer sensitive unspecified EGFR antibody + unspecified ERBB3 antibody Preclinical - Cell culture Actionable In a preclinical study, combination of an unspecified EGFR antibody and an unspecified Erbb3 (Her3) antibody resulted in inhibition of survival in Egfr amplified head and neck cancer cells that developed Erbitux (cetuximab) resistance in culture (PMID: 27196767). 27196767
EGFR amp triple-receptor negative breast cancer sensitive SHP099 Preclinical - Cell culture Actionable In a preclinical study, SHP099 inhibited ERK activation and reduced proliferation of an EGFR-amplified triple-negative breast cancer cell line in culture (PMID: 27362227). 27362227
EGFR amp colorectal cancer sensitive Panitumumab Phase III Actionable In a Phase III study, response to Vectibix (pantitumumab) was associated with EGFR amplification in colorectal cancer patients (PMID: 17664472). 17664472
EGFR amp esophagus squamous cell carcinoma sensitive SHP099 Preclinical - Cell line xenograft Actionable In a preclinical study, SHP099 inhibited ERK activation and reduced proliferation of EGFR-amplified esophageal squamous cell carcinoma cells in culture, and inhibited tumor growth in EGFR-amplified esophageal squamous cell carcinoma cell line xenograft models (PMID: 27362227). 27362227
EGFR amp esophagus squamous cell carcinoma resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, esophagus squamous cell carcinoma cells harboring EGFR amplification demonstrated resistance to Tarceva (erlotinib) in a cell viability assay (PMID: 27207775). 27207775
EGFR amp malignant glioma no benefit Erlotinib + Temsirolimus Phase Ib/II Actionable In a Phase I/II clinical trial, Torisel (temsirolimus) in combination with Tarceva (erlotinib) demostrated minimal efficacy at the maximum tolerated dosage in high-grade glioma patients, with no correlation between EGFR amplification and survival (PMID: 24470557). 24470557
EGFR amp head and neck squamous cell carcinoma sensitive Depatuxizumab mafodotin Preclinical - Cell line xenograft Actionable In a preclinical study, ABT-414 demonstrated cytoxicity against an EGFR-amplified head and neck squamous cell carcinoma (HNSCC) cell line in culture and induced tumor regression in EGFR-amplified HNSCC cell line xenograft models (PMID: 26846818). 26846818
EGFR amp lung non-small cell carcinoma predicted - sensitive Docetaxel + Vandetanib Phase III Actionable In a Phase III trial (ZODIAC), Caprelsa (vandetanib) and Taxotere (docetaxel) combination treatment resulted in improved progression-free survival (HR=0.61), overall survival (HR=0.48), and objective response (odd ratio=3.90) in non-small cell lung cancer patients harboring EGFR amplification compared to the overall study population (PMID: 25057173; NCT00312377). 25057173
EGFR amp head and neck cancer sensitive unspecified EGFR antibody + unspecified IGF-1R antibody Preclinical - Cell culture Actionable In a preclinical study, combination of an unspecified EGFR antibody and an unspecified Igf-1r antibody resulted in growth inhibition in Egfr amplified head and neck cancer cells that developed Erbitux (cetuximab) resistance in culture (PMID: 27196767). 27196767
EGFR amp triple-receptor negative breast cancer sensitive Erlotinib + PF-431396 Preclinical - Cell culture Actionable In a preclinical study, the combination of Tarceva (erlotinib) and PF-431396 resulted in a synergistic effect in a triple-receptor negative breast cancer cell line harboring EGFR amplification, demonstrating inhibition of cell growth in culture (PMID: 27793840). 27793840
EGFR amp head and neck cancer sensitive unspecified EGFR antibody Preclinical - Cell culture Actionable In a preclinical study, combination of two unspecified EGFR antibodies targeting nonoverlapping epitopes of Egfr resulted in Egfr degradation and inhibition of proliferation in Egfr amplified head and neck cancer cells that developed Erbitux (cetuximab) resistance in culture (PMID: 27196767). 27196767
EGFR amp head and neck squamous cell carcinoma resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, head and neck squamous cell carcinoma cells harboring EGFR amplification demonstrated resistance to Tarceva (erlotinib) in a cell viability assay (PMID: 27207775). 27207775
EGFR amp EGFR G696_P1033dup lung adenocarcinoma predicted - resistant Afatinib Case Reports/Case Series Actionable In a clinical case study, a patient with lung adenocarcinoma harboring EGFR G696_P1033dup had a partial response after two cycles of Gilotrif (afatinib), but subsequently developed resistance to the therapy after amplification of EGFR (PMID: 26286086). 26286086
EGFR amp ERBB2 amp MET amp gastric adenocarcinoma predicted - resistant AMG 337 Preclinical - Pdx Actionable In a Phase II clinical trial, a gastric adenocarcinoma patient-derived xenograft (PDX) model with amplification of EGFR, ERBB2 (HER2), and MET demonstrated resistance to treatment with AMG 337 (PMID: 30463996; NCT01522768). 30463996
EGFR amp ERBB2 amp MET amp gastric adenocarcinoma resistant Afatinib Case Reports/Case Series Actionable In a Phase II clinical trial, a metastatic gastric adenocarcinoma patient with co-amplification of EGFR and ERBB2 (HER2) who initially responded to Gilotrif (afatinib) treatment progressed at 12 weeks and was found to have acquired amplification of MET in the progressing sites, which was subsequently confirmed to be associated with resistance via a patient-derived xenograft (PDX) model treated with Gilotrif (afatinib) (PMID: 30463996; NCT01522768). 30463996
EGFR amp ERBB2 amp MET amp gastric adenocarcinoma predicted - sensitive Afatinib + AMG 337 Preclinical - Pdx Actionable In a Phase II clinical trial, preclinical analysis of a gastric adenocarcinoma patient-derived xenograft (PDX) model with amplification of EGFR, ERBB2 (HER2), and MET demonstrated tumor regression when treated with a combination of Gilotrif (afatinib) and AMG 337 (PMID: 30463996; NCT01522768). 30463996
EGFR amp EGFR G719A glioblastoma multiforme sensitive Gefitinib + Linsitinib Preclinical Actionable In a preclinical study, Iressa (gefitinib) and Linsitinib (OSI-906) worked synergistically to inhibit survival of glioblastoma cell lines harboring EGFR amplification and EGFR G719A in culture (PMID: 26561558). 26561558
EGFR amp EGFR G719A glioblastoma multiforme sensitive BMS-754807 + Dacomitinib Preclinical - Cell culture Actionable In a preclinical study, Vizimpro (dacomitinib) and BMS-754807 worked synergistically to inhibit survival of glioblastoma cell lines harboring EGFR amplification and EGFR G719A in culture (PMID: 26561558). 26561558
PDGFRA amp EGFR amp glioblastoma multiforme sensitive Gefitinib + Imatinib Preclinical Actionable In a preclinical study, Gleevec (imatinib) and Iressa (gefitinib) acted synergistically to decrease downstream signaling activity and inhibit cell growth of glioblastoma cell lines with EGFR and PDGFRA coamplification (PMID: 22323597). 22323597
EGFR amp ERBB2 over exp stomach cancer predicted - resistant Trastuzumab Clinical Study - Cohort Actionable In a clinical study (AMNESIA-1), assessment of pre-treatment tumor samples from ERBB2 (HER2)-positive gastric or gastroesophageal cancer patients (defined as HER2 IHC 3+ or HER2 IHC 2+/ISH+) identified EGFR amplification in 2 patients demonstrating primary resistance to Herceptin (trastuzumab) (PMID: 29208673). 29208673
EGFR amp FGFR1 amp lung cancer resistant Erdafitinib Preclinical - Cell culture Actionable In a preclinical study, lung cancer cell lines with co-amplification of FGFR1 and EGFR demonstrated insensitivity to Balversa (erdafitinib) in culture (PMID: 28341788). 28341788
EGFR amp EGFR over exp esophageal cancer sensitive Theliatinib Preclinical - Pdx Actionable In a preclinical study, Theliatinib treatment resulted in tumor regression in patient-derived xenograft (PDX) models of esophageal cancer with both EGFR amplification and Egfr overexpression (PMID: 28881608) 28881608
EGFR amp MET amp lung non-small cell carcinoma predicted - resistant Erlotinib Case Reports/Case Series Actionable In a clinical case study, a patient with non-small cell lung cancer harboring EGFR amplification progressed after Tarceva (erlotinib) treatment, and was found to have acquired a MET amplification (PMID: 30268451). 30268451
EGFR amp MET amp lung non-small cell carcinoma predicted - resistant Gefitinib Case Reports/Case Series Actionable In a clinical case study, a patient with non-small cell lung cancer harboring EGFR amplification progressed after Iressa (gefitinib) treatment, and was found to have acquired MET amplification (PMID: 30268451). 30268451
EGFR amp MET amp esophagus adenocarcinoma sensitive Crizotinib + Lapatinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Xalkori (crizotinib) and Tykerb (lapatinib) worked synergistically to inhibit growth of an esophageal adenocarcinoma cell line with EGFR and MET copy number gain in culture (PMID: 27595477). 27595477
EGFR amp MET amp lung non-small cell carcinoma predicted - resistant Osimertinib Case Reports/Case Series Actionable In a clinical case study, two patients with non-small cell lung cancer harboring EGFR amplification and EGFR T790M progressed after Tagrisso (osimertinib) treatment, and were found to have lost the EGFR T790M and acquired MET amplification (PMID: 30268451). 30268451
EGFR amp EGFR E746_A750del EGFR T790M lung non-small cell carcinoma resistant Rociletinib Preclinical - Cell culture Actionable In a preclinical study, acquired resistance to Rociletinib (CO-1686) treatment in non-small cell lung cancer cells harboring EGFR E746_A750del and EGFR T790M in culture was associated with EGFR amplification and reduced expression of EGFR E746_A750del and EGFR T790M, and proliferation and EGFR pathway signaling were maintained upon Rociletinib (CO-1686) treatment in culture (PMID: 30322949). 30322949
EGFR amp EGFR E746_A750del EGFR T790M lung non-small cell carcinoma sensitive Afatinib + Cetuximab Preclinical - Cell culture Actionable In a preclinical study, a Rociletinib (CO-1686)-resistant non-small cell lung cancer cell line harboring EGFR E746_A750del and EGFR T790M with EGFR amplification, which demonstrated reduced expression of EGFR E746_A750del and EGFR T790M relative to the parental cell line, exhibited reduced proliferation and increased apoptosis in response to combined Gilotrif (afatinib) and Erbitux (cetuximab) treatment relative to Gilotrif (afatinib) alone in culture (PMID: 30322949). 30322949
EML4-ALK EGFR amp lung non-small cell carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK treated with Xalkori (crizotinib) responded, but eventually progressed, and was subsequently found to harbor a presumed resistance alteration, EGFR amplification (PMID: 29636358). 29636358
EGFR amp EGFR S492R BRAF V600E colorectal cancer resistant Cetuximab Case Reports/Case Series Actionable In a clinical study, EGFR S492R was detected in the post-Erbitux (cetuximab) sample from a colorectal cancer patient harboring EGFR amplification and BRAF V600E who progressed on an Erbitux (cetuximab) regimen (PMID: 22270724). 22270724
EGFR amp EGFR S492R colorectal cancer predicted - sensitive Panitumumab Case Reports/Case Series Actionable In a clinical study, a colorectal cancer patient harboring both EGFR amplification and EGFR S492R demonstrated a greater than 50% reduction in liver lesion volume when treated with Vectibix (panitumumab) (PMID: 22270724). 22270724
EGFR amp EGFR S492R colorectal cancer resistant Cetuximab Case Reports/Case Series Actionable In a clinical study, EGFR S492R was detected in a colorectal cancer patient harboring EGFR amplification who progressed on an Erbitux (cetuximab) containing regimen, and resistance to Erbitux (cetuximab) was supported by lack of growth inhibition in colorectal cancer cells harboring EGFR S492R and EGFR amplification in culture (PMID: 22270724). 22270724
EGFR amp ERBB2 amp gastric adenocarcinoma predicted - sensitive Afatinib Case Reports/Case Series Actionable In a Phase II clinical trial, a metastatic gastric adenocarcinoma patient with co-amplification of EGFR and ERBB2 (HER2) demonstrated a 43% tumor regression by RECIST when treated with Gilotrif (afatinib) (PMID: 30463996; NCT01522768). 30463996
EGFR amp ERBB2 amp urinary bladder cancer sensitive Afatinib Phase II Actionable In a Phase II clinical trial, two urothelial carcinoma patients with ERBB2 (HER2) and EGFR co-amplification had improved progression free survival when treated with Gilotrif (afatinib), and median PFS was 6.6 months for patients with ERBB2 or ERBB3 alterations relative to 1.4 months for patients lacking alterations (PMID: 27044931). 27044931
EGFR amp ERBB2 amp stomach cancer predicted - sensitive Afatinib Case Reports/Case Series Actionable In a Phase II clinical trial, a gastric cancer patient with co-amplification of EGFR and ERBB2 (HER2) who previously progressed on a combination therapy with Herceptin (trastuzumab) demonstrated a 37% tumor regression when treated with Gilotrif (afatinib) (PMID: 30463996; NCT01522768). 30463996
EGFR amp ERBB2 amp gastric adenocarcinoma predicted - resistant Fluorouracil + Oxaliplatin + Trastuzumab Case Reports/Case Series Actionable In Phase II clinical trial, a patient with metastatic gastric adenocarcinoma progressed while on the combination therapy of Adrucil (fluorouracil), Eloxatin (oxaliplatin), and Herceptin (trastuzumab), and was subsequently found to have acquired co-amplification of EGFR and ERBB2 (HER2) in the liver metastasis (PMID: 30463996; NCT01522768). 30463996
EGFR amp ERBB2 amp stomach cancer predicted - resistant Fluorouracil + Oxaliplatin + Trastuzumab Phase II Actionable In a Phase II clinical trial, co-amplification of EGFR and ERBB2 (HER2) was identified at the time of progression in a patient with ERBB2 (HER2)-positive gastric cancer who initially demonstrated a short response to the combination therapy of Herceptin (trastuzumab), Adrucil (fluorouracil), and Eloxatin (oxaliplatin), but then progression at 7 months (PMID: 30463996; NCT01522768). 30463996
BRAF V600E EGFR amp colorectal cancer resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment were resistant to Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF V600E EGFR amp colorectal cancer resistant Selumetinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment in culture, likely due to the acquired EGFR amplification (PMID: 27312529). 27312529
BRAF V600E EGFR amp colorectal cancer resistant Cetuximab + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment were resistant to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E EGFR amp colorectal cancer resistant Cetuximab + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment were resistant to Erbitux (cetuximab) and Zelboraf (vemurafenib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E EGFR amp colorectal cancer resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment were resistant to Erbitux (cetuximab) in culture (PMID: 27312529). 27312529
BRAF V600E EGFR amp colorectal cancer resistant SCH772984 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment were resistant to SCH772984 in culture (PMID: 27312529). 27312529
BRAF V600E EGFR amp colorectal cancer resistant Dabrafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment were resistant to combination therapy consisting of Tafinlar (dabrafenib) and Mekinist (trametinib) in culture (PMID: 27312529). 27312529
BRAF V600E EGFR amp colorectal cancer sensitive Cetuximab + Dabrafenib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E EGFR amp colorectal cancer resistant Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) in culture (PMID: 27312529). 27312529
BRAF V600E EGFR amp colorectal cancer sensitive Cetuximab + Selumetinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Selumetinib (AZD6244), and Zelboraf (vemurafenib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E EGFR amp colorectal cancer resistant Selumetinib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment were resistant to Selumetinib (AZD6244) in culture (PMID: 27312529). 27312529
EGFR amp PTEN loss glioblastoma multiforme decreased response Dacomitinib Preclinical - Pdx & cell culture Actionable In a preclinical study, patient-derived EGFR amplified glioblastoma cells harboring PTEN loss demonstrated reduced sensitivity to Vizimpro (dacomitinib) induced growth inhibition in culture and in xenograft models (PMID: 25939761). 25939761
EGFR D770_N771insGF lung non-small cell carcinoma predicted - sensitive Luminespib Phase II Actionable In a Phase II trial, Luminespib (AUY922) treatment demonstrated safety and efficacy in patients with advanced non-small cell lung cancer harboring EGFR exon 20 insertions, with 1 patient harboring EGFR D770_N771insGF achieved partial response (PMID: 30351341; NCT01854034). 30351341
EGFR V851I Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR V851I were sensitive to treatment with Tagrisso (osimertinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR V851I Advanced Solid Tumor resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR V851I were resistant to treatment with Tarceva (erlotinib) in culture (PMID: 29141884). 29141884
EGFR V851I Advanced Solid Tumor resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR V851I were resistant to treatment with Erbitux (cetuximab) in culture (PMID: 29141884). 29141884
EGFR V851I Advanced Solid Tumor resistant Gefitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR V851I were resistant to treatment with Iressa (gefitinib) in culture (PMID: 29141884). 29141884
EGFR R451C colorectal cancer sensitive Cetuximab Preclinical Actionable In a preclinical study, Erbitux (cetuximab) inhibited survival of colorectal cancer cell lines over expressing EGFR R451C in culture (PMID: 26843189). 26843189
EGFR R451C Advanced Solid Tumor predicted - sensitive SYM004 Preclinical - Cell culture Actionable In a preclinical study, SYM004 inhibited phosphorylation of EGFR in cells expressing EGFR R451C in culture (PMID: 26888827). 26888827
EGFR R451C colorectal cancer sensitive MM-151 Preclinical Actionable In a preclinical study, MM-151 inhibited survival of colorectal cancer cell lines over expressing EGFR R451C in culture (PMID: 26843189). 26843189
EGFR R451C colorectal cancer sensitive Panitumumab Preclinical Actionable In a preclinical study, Vectibix (panitumumab) inhibited survival of colorectal cancer cell lines over expressing EGFR R451C in culture (PMID: 26843189). 26843189
EGFR D761Y EGFR L858R Advanced Solid Tumor sensitive EKI-285 Preclinical Actionable In a preclinical study, EKI-285 (CL-387,785) inhibited growth of transformed cells expressing EGFR L858R and EGFR D716Y in culture (PMID: 17085664). 17085664
EGFR D761Y EGFR L858R Advanced Solid Tumor decreased response Neratinib Preclinical Actionable In a preclinical study, transformed cells expressing EGFR L858R and D761Y demonstrated decreased sensitivity to Nerlynx (neratinib) in culture (PMID: 17085664). 17085664
EGFR D761Y EGFR L858R Advanced Solid Tumor decreased response Gefitinib Preclinical Actionable In a preclinical study, transformed cells expressing EGFR L858R and EGFR D761Y demonstrated decreased sensitivity to Iressa (gefitinib) in culture (PMID: 17085664). 17085664
EGFR D761Y EGFR L858R lung non-small cell carcinoma predicted - resistant Gefitinib Case Reports/Case Series Actionable In a clinical case study, a patient with EGFR L858R-mutant non-small lung cancer that developed resistance to Iressa (gefitinib) was demonstrated to have acquired a secondary EGFR D761Y mutation (PMID: 17085664). 17085664
EGFR A216T EGFR E746_S752delinsV Advanced Solid Tumor sensitive Gefitinib Preclinical - Cell culture Actionable In a preclinical study, treatment with Iressa (gefitinib) resulted in decreased growth of transformed cells expressing EGFR A216T and EGFR E746_S752delinsV in cis and trans in culture (PMID: 29141884). 29141884
EGFR A216T EGFR E746_S752delinsV Advanced Solid Tumor sensitive Erlotinib Preclinical - Cell culture Actionable In a preclinical study, treatment with Tarceva (erlotinib) resulted in decreased growth of transformed cells expressing EGFR A216T and EGFR E746_S752delinsV in cis and trans in culture (PMID: 29141884). 29141884
EGFR A216T EGFR E746_S752delinsV Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, treatment with Tagrisso (osimertinib) resulted in decreased growth of transformed cells expressing EGFR A216T and EGFR E746_S752delinsV in cis and trans in culture (PMID: 29141884). 29141884
EGFR A216T EGFR E746_S752delinsV Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, treatment with Gilotrif (afatinib) resulted in decreased growth of transformed cells expressing EGFR A216T and EGFR E746_S752delinsV in cis and trans in culture (PMID: 29141884). 29141884
EGFR A216T EGFR E746_S752delinsV Advanced Solid Tumor resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A216T and EGFR E746_S752delinsV in cis and trans in culture demonstrated resistance to treatment with Erbitux (cetuximab) (PMID: 29141884). 29141884
EGFR A216T Advanced Solid Tumor sensitive Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A216T were sensitive to treatment with Erbitux (cetuximab) in culture (PMID: 29141884). 29141884
EGFR A216T Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A216T were sensitive to treatment with Gilotrif (afatinib) in culture (PMID: 29141884). 29141884
EGFR A216T Advanced Solid Tumor sensitive Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A216T were sensitive to treatment with Tarceva (erlotinib) in culture (PMID: 29141884). 29141884
EGFR A216T Advanced Solid Tumor sensitive Gefitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A216T were sensitive to treatment with Iressa (gefitinib) in culture (PMID: 29141884). 29141884
EGFR A216T Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A216T were sensitive to treatment with Tagrisso (osimertinib) in culture (PMID: 29141884). 29141884
EGFR L747_T751del EGFR S752I lung non-small cell carcinoma sensitive Trametinib + WZ4002 Preclinical - Cell culture Actionable In a preclinical study, the addition of Mekinist (trametinib) to WZ4002 treatment did not significantly impact cell viability compared to WZ4002 alone, but delayed onset of drug resistance in a non-small cell lung cancer cell line harboring EGFR L747_T751del and EGFR S752I in culture (PMID: 26036643). 26036643
EGFR L747_T751del Advanced Solid Tumor sensitive Rociletinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR L747_T751del were sensitive to treatment with Rociletinib (CO-1686) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR L747_T751del Advanced Solid Tumor sensitive Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR L747_T751del were sensitive to treatment with Tarceva (erlotinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR L747_T751del Advanced Solid Tumor sensitive Gefitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR L747_T751del were sensitive to treatment with Iressa (gefitinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR L747_T751del Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR L747_T751del were sensitive to treatment with Gilotrif (afatinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR L747_T751del Advanced Solid Tumor resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR L747_T751del were resistant to treatment with Erbitux (cetuximab) in culture (PMID: 29141884). 29141884
EGFR exon 20 ins Advanced Solid Tumor resistant Osimertinib Preclinical Actionable In a preclinical study, cells expressing an EGFR exon 20 insertion mutation were resistant to AZD9291 in culture (PMID: 24893891). 24893891
EGFR exon 20 ins Advanced Solid Tumor sensitive DZD9008 Preclinical - Pdx & cell culture Actionable In a preclinical study, DZD9008 inhibited proliferation of tumor cells expressing EGFR exon 20 insertions in culture, resulted in tumor growth inhibition and regression in patient-derived xenograft (PDX) models (AACR Annual Meeting 2019, Abstract 3081). detail...
EGFR exon 20 ins lung non-small cell carcinoma predicted - sensitive Poziotinib Phase II Actionable In a Phase II trial, Poziotinib (HM781-36B) treatment resulted in an overall response rate of 73% (8/11) in non-small cell lung carcinoma patients harboring EGFR exon 20 insertions (PMID: 29162564). 29162564 detail...
EGFR exon 20 ins Advanced Solid Tumor sensitive AP32788 Preclinical - Pdx & cell culture Actionable In a preclinical study, AP32788 inhibited growth of transformed cell lines over expressing EGFR exon 20 insertions in culture, and induced tumor regression in PDX models (AACR, Cancer Res: April 2016; Volume 57, Abstract #2644). detail...
EGFR exon 20 ins lung non-small cell carcinoma decreased response Icotinib Clinical Study - Cohort Actionable In a retrospective analysis, non-small cell lung cancer patients with EGFR exon 20 insertions (n=29) demonstrated inferior progression-free survival following treatment with first-generation EGFR tyrosine kinase inhibitors such as Iressa (gefitinib), Tarceva (erlotinib), or Icotinib (1.9 months vs. 10.8 months) compared to patients with EGFR L858R and exon 19 deletion mutations (n=592)(PMID: 27468240). 27468240
EGFR exon 20 ins lung non-small cell carcinoma decreased response Icotinib Clinical Study Actionable In a retrospective analysis, non-small cell lung cancer patients harboring EGFR exon 20 insertions demonstrated a response rate of 11.11% and disease control rate of 44.44%, and a median progression-free survival of 1.9 months following treatment with icotinib (J Clin Oncol 35, 2017 (suppl; abstr e14050)). detail...
EGFR exon 20 ins lung non-small cell carcinoma resistant Gefitinib Case Reports/Case Series Actionable In a retrospective analysis, non-small cell lung cancer patients harboring EGFR exon 20 insertions displayed progressive disease following treatment with Iressa (gefitinib), and resistance to Iressa (gefitinib) was replicated in cell culture studies (PMID: 24353160). 24353160
EGFR exon 20 ins lung non-small cell carcinoma resistant Gefitinib Clinical Study - Cohort Actionable In a retrospective analysis, non-small cell lung cancer patients with EGFR exon 20 insertions (n=29) demonstrated inferior progression-free survival following treatment with first-generation EGFR tyrosine kinase inhibitors such as Iressa (gefitinib), Tarceva (erlotinib), or Icotinib (1.9 months vs. 10.8 months) compared to patients with EGFR L858R and exon 19 deletion mutations (n=592)(PMID: 27468240). 27468240
EGFR exon 20 ins Advanced Solid Tumor resistant Rociletinib Preclinical Actionable In a preclinical study, cells expressing an EGFR exon 20 insertion demonstrated resistance to Rociletinib (CO-1686) in culture (PMID: 24065731). 24065731
EGFR exon 20 ins lung cancer predicted - sensitive Tarloxotinib Preclinical - Pdx & cell culture Actionable In a preclinical study, processed Tarloxotinib (TRLX) inhibited Egfr signaling and proliferation of patient-derived lung cancer cells harboring EGFR exon 20 insertions in culture, and the prodrug Tarloxotinib (TRLX) resulted in tumor regression in patient-derived xenograft (PDX) models (Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A157). detail...
EGFR exon 20 ins lung non-small cell carcinoma resistant Afatinib Phase II Actionable In a post-hoc analysis of Phase II and Phase III trials (LUX-Lung2, LUX-Lung 3, LUX-Lung 6), Gilotrif (afatinib) treatment resulted in an objective response rate of 8.7% (2/23) in non-small cell lung cancer patients harboring EGFR exon 20 insertions, with a mean progression-free survival of 2.7 months, and an overall survival of 9.2 months (PMID: 26051236; NCT00525148, NCT00949650, and NCT01121393). 26051236
EGFR exon 20 ins lung non-small cell carcinoma resistant Afatinib Preclinical Actionable In a preclinical study, non-small cell carcinoma cell lines harboring EGFR exon 20 insertions demonstrated resistance to Gilotrif (afatinib) in cell culture (PMID: 24353160). 24353160
EGFR exon 20 ins lung non-small cell carcinoma resistant Afatinib Case Reports/Case Series Actionable In a clinical study, Gilotrif (afatinib) treatment resulted in partial response in 33% (1/3), stable disease in 33% (1/3), and progressive disease in 337% (1/3) in non-small cell lung carcinoma patients harboring an EGFR exon 20 insertion mutation (PMID: 26354527). 26354527
EGFR exon 20 ins lung non-small cell carcinoma predicted - sensitive Luminespib Case Reports/Case Series Actionable In a clinical case study, treatment with Luminespib (AUY922) on a clinical trial resulted in a partial response in a non-small cell lung cancer patient harboring an EGFR exon 20 insertion (PMID: 30154228; NCT01124864). 30154228
EGFR exon 20 ins lung non-small cell carcinoma predicted - sensitive Luminespib Phase II Actionable In a Phase II trial, Luminespib (AUY922) demonstrated safety and preliminary efficacy in EGFR TKI-resistant non-small cell lung cancer patients harboring EGFR exon 20 insertions, with 10% (1/10) of patients achieving partial response and 30% of (3/10) patients achieving stable disease, and a median progression-free survival of 6.1 months (J Clin Oncol 33, 2015 (suppl; abstr 8015)). detail...
EGFR exon 20 ins lung non-small cell carcinoma predicted - sensitive Luminespib Phase II Actionable In a Phase II trial, Luminespib (AUY922) treatment resulted in partial response or stable disease over 3 months in 38% (11/29) of patients with advanced non-small cell lung cancer harboring EGFR exon 20 insertions, with an objective response rate of 17% (5/29), a median progression-free survival of 2.9 months, and a medial overall survival of 13 months (PMID: 30351341; NCT01854034). 30351341
EGFR exon 20 ins Advanced Solid Tumor predicted - sensitive TAS6417 Preclinical - Cell culture Actionable In a preclinical study, TAS6417 inhibited growth of transformed cells expressing EGFR exon 20 insertions in culture (Proceedings of the American Association for Cancer Research, Vol 60, Mar 2019, Abstract #1329). detail...
EGFR exon 20 ins Advanced Solid Tumor predicted - sensitive Nazartinib Preclinical - Cell culture Actionable In a preclinical study, EGF816 inhibited growth of transformed cell lines expressing three different EGFR exon 20 insertions in culture (PMID: 26825170). 26825170
EGFR exon 20 ins Advanced Solid Tumor resistant Dacomitinib Preclinical Actionable In a preclinical study, transformed cells expressing an EGFR exon 20 insertion mutation had decreased response to Vizimpro (dacomitinib) compared to other EGFR activating mutations, with inhibitory doses exceeding clinically attainable levels (PMID: 18089823, PMID: 21764376). 18089823 21764376
EGFR exon 20 ins lung non-small cell carcinoma resistant Erlotinib Case Reports/Case Series Actionable In a retrospective analysis, non-small cell lung cancer patients harboring EGFR exon 20 insertions displayed progressive disease following treatment with Tarceva (erlotinib), and resistance to Tarceva (erlotinib) was replicated in cell culture studies (PMID: 24353160). 24353160
EGFR exon 20 ins lung non-small cell carcinoma resistant Erlotinib Clinical Study - Cohort Actionable In a retrospective analysis, non-small cell lung cancer patients with EGFR exon 20 insertions (n=29) demonstrated inferior progression-free survival following treatment with first-generation EGFR tyrosine kinase inhibitors such as Iressa (gefitinib), Tarceva (erlotinib), or Icotinib (1.9 months vs. 10.8 months) compared to patients with EGFR L858R and exon 19 deletion mutations (n=592)(PMID: 27468240). 27468240
EGFR A750P EGFR L747_E749del PIK3CA E545K lung non-small cell carcinoma decreased response Osimertinib Preclinical - Cell culture Actionable In a preclinical study, overexpression of PIK3CA E545K in a non-small cell lung cancer cell line harboring EGFR L747_E749del and EGFR A750P resulted in decreased sensitivity to Tagrisso (osimertinib) in culture (PMID: 30228210). 30228210
EGFR A750P EGFR L747_E749del lung non-small cell carcinoma sensitive Trametinib + WZ4002 Preclinical - Cell culture Actionable In a preclinical study, the addition of Mekinist (trametinib) to WZ4002 treatment did not significantly impact cell viability compared to WZ4002 alone, but delayed onset of drug resistance in a non-small cell lung cancer cell line harboring EGFR A750P and EGFR L747_E749del in culture (PMID: 26036643). 26036643
EGFR E804G EGFR P699L lung adenocarcinoma predicted - resistant Gefitinib Case Reports/Case Series Actionable In a clinical case study, Iressa (gefitinib) treatment resulted in rapid disease progression in a patient with lung adenocarcinoma harboring EGFR E804G and P699L (PMID: 22722798). 22722798
EGFR L747_S752del EGFR T790M lung adenocarcinoma predicted - resistant Erlotinib Case Reports/Case Series Actionable In a retrospective analysis, a patient with lung adenocarcinoma harboring EGFR L747_S752del and EGFR T790M, who was found to have acquired an EGFR T790M mutation upon disease progression on Iressa (gefitinib), had rapid disease progression in response to Tarceva (erlotinib) therapy (PMID: 18981003). 18981003
EGFR L747_S752del EGFR T790M lung adenocarcinoma predicted - resistant Gefitinib Case Reports/Case Series Actionable In a retrospective analysis, a patient with lung adenocarcinoma harboring EGFR L747_S752del that developed Iressa (gefitinib) resistance after an initial response was demonstrated to have acquired an EGFR T790M mutation (PMID: 18981003). 18981003
EGFR L747_S752del lung adenocarcinoma predicted - sensitive Gefitinib Case Reports/Case Series Actionable In a retrospective analysis, a patient with lung adenocarcinoma harboring EGFR L747_S752del had a complete response with a 24-month progression-free survival in response to Iressa (gefitinib) therapy (PMID: 18981003). 18981003
EGFR I744M Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR I744M were sensitive to treatment with Gilotrif (afatinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR I744M Advanced Solid Tumor resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR I744M were resistant to treatment with Erbitux (cetuximab) in culture (PMID: 29141884). 29141884
EGFR K739_I744dup lung non-small cell carcinoma predicted - sensitive Gefitinib Case Reports/Case Series Actionable In a clinical study, Iressa (gefitinib) demonstrated some efficacy in two patients with non-small cell lung cancer each harboring EGFR K739_I744dup (reported as I744_K745insKIPVAI), including a partial response in one patient and stable disease in the other patient (PMID: 28089594). 28089594
EGFR K739_I744dup lung adenocarcinoma predicted - sensitive Erlotinib Case Reports/Case Series Actionable In a clinical study, a patient with lung adenocarcinoma harboring EGFR K739_I744dup (reported as I744_K745insKIPVAI) demonstrated a partial response when treated with Tarceva (erlotinib) (PMID: 22190593). 22190593
EGFR K714R Advanced Solid Tumor sensitive Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR K714R were sensitive to treatment with Erbitux (cetuximab) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR K714R Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR K714R were sensitive to treatment with Gilotrif (afatinib) in culture (PMID: 29141884). 29141884
EGFR K714R EGFR L858R Advanced Solid Tumor resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR K714R and EGFR L858R in cis and trans were resistant to Erbitux (cetuximab) in culture (PMID: 29141884). 29141884
EGFR K714R EGFR L858R Advanced Solid Tumor sensitive Erlotinib Preclinical - Cell culture Actionable In a preclinical study, treatment with Tarceva (erlotinib) resulted in decreased growth of transformed cells expressing EGFR K714R and EGFR L858R in cis and trans in culture (PMID: 29141884). 29141884
EGFR K714R EGFR L858R Advanced Solid Tumor sensitive Gefitinib Preclinical - Cell culture Actionable In a preclinical study, treatment with Iressa (gefitinib) resulted in decreased growth of transformed cells expressing EGFR K714R and EGFR L858R in cis and trans in culture (PMID: 29141884). 29141884
EGFR K714R EGFR L858R Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, treatment with Tagrisso (osimertinib) resulted in decreased growth of transformed cells expressing EGFR K714R and EGFR L858R in cis and trans in culture (PMID: 29141884). 29141884
EGFR D770_N771insGV lung non-small cell carcinoma predicted - sensitive Luminespib Phase II Actionable In a Phase II trial, Luminespib (AUY922) treatment demonstrated safety and efficacy in patients with advanced non-small cell lung cancer harboring EGFR exon 20 insertions, with 1 patient harboring EGFR D770_N771insGV achieved stable disease (PMID: 30351341; NCT01854034). 30351341
EGFR E746_A750del EML4-ALK lung non-small cell carcinoma predicted - resistant Osimertinib Case Reports/Case Series Actionable In a clinical study, EML4-ALK was identified as an acquired resistance mutation in a patient with non-small cell lung cancer harboring EGFR E746_A750del, whose disease progressed after initial response to Tarceva (erlotinib) followed by Tagrisso (osimertinib) (PMID: 29883838). 29883838
EGFR E746_A750del EGFR T790M EGFR Q791R Advanced Solid Tumor sensitive Osimertinib Preclinical Actionable In a preclinical study, AZD9291 inhibited growth of transformed cells expressing an EGFR E746_A750del/EGFR T790M/EGFR Q791R triple mutation in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR T790M EGFR Q791R Advanced Solid Tumor resistant Rociletinib Preclinical Actionable In a preclinical study, transformed cells expressing an EGFR E746_A750del/EGFR T790M/EGFR Q791R triple mutation demonstrated resistance to Rociletinib (CO-1686) in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR T790M EGFR C797S Advanced Solid Tumor predicted - sensitive TQB3804 Preclinical - Cell line xenograft Actionable In a preclinical study, TQB3804 inhibited Egfr downstream signaling, resulted in growth inhibition of transformed cells expressing EGFR E746_A750del, T790M, and C797S triple mutations in culture and in cell line xenograft models (Proceedings of the American Association for Cancer Research, Vol 60, Mar 2019, Abstract #1320). detail...
EGFR E746_A750del EGFR T790M EGFR C797S Advanced Solid Tumor no benefit Cetuximab Preclinical - Cell culture Actionable In a preclinical study, Erbitux (cetuximab) did not inhibit growth of transformed cells expressing a EGFR E746_A750del/T790M/C797S triple mutation in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR T790M EGFR C797S lung non-small cell carcinoma predicted - sensitive TQB3804 Preclinical - Pdx & cell culture Actionable In a preclinical study, TQB3804 inhibited Egfr downstream signaling, resulted in growth inhibition of non-small cell lung cancer cell lines harboring EGFR E746_A750del, T790M, and C797S triple mutations in culture and in cell line xenograft models, and inhibited tumor growth in a patient-derived xenograft (PDX) model (Proceedings of the American Association for Cancer Research, Vol 60, Mar 2019, Abstract #1320). detail...
EGFR E746_A750del EGFR L844V Advanced Solid Tumor resistant Rociletinib Preclinical Actionable In a preclinical study, transformed cells expressing an EGFR E746_A750del/EGFR L844V double mutation demonstrated resistance to Rociletinib (CO-1686) in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR L844V Advanced Solid Tumor sensitive Osimertinib Preclinical Actionable In a preclinical study, AZD9291 inhibited growth of transformed cells expressing an EGFR E746_A750del/EGFR L844V double mutation in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR L844V Advanced Solid Tumor sensitive Afatinib Preclinical Actionable In a preclinical study, Gilotrif (afatinib) inhibited growth of transformed cells expressing an EGFR E746_A750del/EGFR L844V double mutation in culture (PMID: 25948633). 25948633
EGFR E746_A750del FGFR3-TACC3 lung non-small cell carcinoma predicted - resistant Naquotinib Case Reports/Case Series Actionable In a clinical study, FGFR3-TACC3 was identified as an acquired resistance mutation in a patient with non-small cell lung cancer harboring EGFR E746_A750del, whose disease progressed after initial response to Tarceva (erlotinib) followed by Naquotinib (ASP8273) (PMID: 29883838). 29883838
EGFR E746_A750del FGFR3-TACC3 lung non-small cell carcinoma predicted - resistant Osimertinib Case Reports/Case Series Actionable In a clinical study, FGFR3-TACC3 was identified as an acquired resistance mutation in a patient with non-small cell lung cancer harboring EGFR E746_A750del, whose disease progressed after initial response to Tarceva (erlotinib), followed by Tagrisso (osimertinib) (PMID: 29883838). 29883838
EGFR E746_A750del FGFR3-TACC3 lung non-small cell carcinoma predicted - resistant Afatinib Case Reports/Case Series Actionable In a clinical study, FGFR3-TACC3 was identified as an acquired resistance mutation in a patient with non-small cell lung cancer harboring EGFR E746_A750del, whose disease progressed after initial response to Gilotrif (afatinib) (PMID: 29883838). 29883838
EGFR E746_A750del lung non-small cell carcinoma sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, Gilotrif (afatinib) inhibited EGFR signaling and proliferation of non-small cell lung cancer cells harboring EGFR E746_A750del in culture (PMID: 29467275). 29467275
EGFR E746_A750del Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EGFR E746_A750del in culture (PMID: 27780853). 27780853
EGFR E746_A750del lung non-small cell carcinoma sensitive Dacomitinib Phase II Actionable In a Phase II clinical trial, 74% (34/46) of patients with EGFR exon 19 or 21 mutant lung cancers had partial response (PFS average= 17 months) to first line treatment with Vizimpro (dacomitinib) (J Clin Oncol 30, 2012 (suppl; abstr 7530)). detail...
EGFR E746_A750del lung non-small cell carcinoma resistant Lapatinib Preclinical Actionable In a preclinical study, non-small cell lung carcinoma cells harboring EGFR E746_A750del demonstrated resistance to growth inhibition by Tykerb (lapatinib) in cell culture (PMID: 18199554). 18199554
EGFR E746_A750del lung non-small cell carcinoma sensitive Naquotinib Preclinical - Cell culture Actionable In a preclinical study, Naquotinib (ASP8273) inhibited EGFR signaling and proliferation of non-small cell lung cancer cells harboring EGFR E746_A750del in culture (PMID: 29467275). 29467275
EGFR E746_A750del lung adenocarcinoma predicted - sensitive Gefitinib Clinical Study Actionable In a retrospective analysis, treatment with Iressa (gefitinib) was found to result in partial response in 7 patients, stable disease in 1 patient, and progressive disease in 1 patient with lung adenocarcinoma harboring EGFR E746_A750del (PMID: 18981003). 18981003
EGFR E746_A750del lung non-small cell carcinoma sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, Tagrisso (osimertinib) inhibited EGFR signaling and proliferation of non-small cell lung cancer cells harboring EGFR E746_A750del in culture (PMID: 29467275). 29467275
EGFR E746_A750del lung cancer sensitive TAS6417 Preclinical - Cell culture Actionable In a preclinical study, TAS6417 inhibited growth of lung cancer cell lines harboring EGFR E746_A750del in culture (PMID: 29748209). 29748209
EGFR E746_A750del lung non-small cell carcinoma sensitive Erlotinib Preclinical - Cell culture Actionable In a preclinical study, Tarceva (erlotinib) inhibited EGFR signaling and proliferation of non-small cell lung cancer cells harboring EGFR E746_A750del in culture (PMID: 29467275). 29467275
EGFR E746_A750del lung non-small cell carcinoma sensitive Vandetanib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells harboring EGFR E746_A750del demonstrated increased sensitivity to Caprelsa (vandetanib) in culture (PMID: 15604279). 15604279
EGFR E746_A750del Advanced Solid Tumor sensitive Vandetanib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR E746_A750del demonstrated increased sensitivity to Caprelsa (vandetanib) in culture (PMID: 15604279). 15604279
EGFR E746_A750del lung carcinoma sensitive BGB-283 Preclinical - Cell line xenograft Actionable In a preclinical study, BGB-283 inhibited Egfr phosphorylation and cell proliferation in lung carcinoma cells harboring EGFR E746_A750del in culture, and resulted in tumor regression in cell line xenograft models (PMID: 26208524). 26208524
EGFR E746_A750del lung non-small cell carcinoma sensitive Cisplatin + ER2 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of ER2 and Platinol (cisplatin) demonstrated synergy in inhibiting tumor growth in a non-small cell lung cancer cell line xenograft model harboring EGFR E746_A750del (PMID: 27040853). 27040853
EGFR E746_A750del lung adenocarcinoma sensitive Avitinib maleate Preclinical - Cell line xenograft Actionable In a preclinical study, lung adenocarcinoma cells harboring EGFR E746_A750del demonstrated sensitivity to treatment with Avitinib maleate (AC0010), which resulted in inhibition of both cell growth and Egfr phosphorylation in culture, and tumor regression in xenograft models (PMID: 27573423). 27573423
EGFR E746_A750del lung non-small cell carcinoma sensitive Erlotinib + Ganetespib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Ganetespib and Tarceva (erlotinib) demonstrated improved antitumor activity compared to either agent alone in cell line xenograft models of non-small cell lung cancer harboring EGFR E746_A750del (PMID: 25077897). 25077897
EGFR E746_A750del lung non-small cell carcinoma sensitive Trametinib + WZ4002 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of WZ4002 and Mekinist (trametinib) inhibited tumor growth, and resulted in reduced tumor rebound compared to WZ4002 alone in non-small cell lung cancer cell line xenograft models harboring EGFR E746_A750del (PMID: 26036643). 26036643
EGFR E746_A750del lung non-small cell carcinoma sensitive ER2 Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with ER2 resulted in decreased proliferation and increased apoptosis of non-small cell lung cancer (NSCLC) cells harboring EGFR E746_A750del in culture, and delayed tumor growth in NSCLC cell line xenograft models with EGFR E746_A750del (PMID: 27040853). 27040853
EGFR E746_A750del lung non-small cell carcinoma sensitive Gedatolisib Preclinical Actionable In a preclinical study, Gedatolisib (PKI-587) inhibited growth of human non-small cell lung carcinoma cells harboring EGFR E746_A750del in culture (PMID: 21325073, PMID: 16731747). 21325073 16731747
BRAF V600E EGFR E746_A750del lung non-small cell carcinoma predicted - sensitive Dabrafenib + Osimertinib Case Reports/Case Series Actionable In a clinical case study, a patient with advanced non-small cell lung cancer who lost EGFR T790M, but still harbors EGFR E746_A750del and acquired BRAF V600E demonstrated an improved metabolic response when treated with the combination therapy of Sprycel (dabrafenib) and Tagrisso (osimertinib) (Journal of Clinical Oncology, 2019, 37, no. 15_suppl). detail...
BRAF V600E EGFR E746_A750del lung non-small cell carcinoma predicted - resistant Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, a patient with advanced non-small cell lung cancer who lost EGFR T790M, but still harbors EGFR E746_A750del and acquired BRAF V600E demonstrated continued progression while being treated with the combination therapy of Sprycel (dabrafenib) and Mekinist (trametinib) (Journal of Clinical Oncology, 2019, 37, no. 15_suppl). detail...
EGFR E746_A750del EGFR T790M EGFR L844V Advanced Solid Tumor resistant Rociletinib Preclinical Actionable In a preclinical study, transformed cells expressing an EGFR E746_A750del/EGFR T790M/EGFR L844V triple mutation demonstrated resistance to Rociletinib (CO-1686) in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR T790M EGFR L844V Advanced Solid Tumor sensitive Osimertinib Preclinical Actionable In a preclinical study, AZD9291 inhibited growth of transformed cells expressing an EGFR E746_A750del/EGFR T790M/EGFR L844V triple mutation in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR T790M EGFR L844V lung non-small cell carcinoma sensitive Osimertinib Preclinical Actionable In a preclinical study, AZD9291 inhibited growth of non-small cell lung cancer cells harboring EGFR E746_A750del and EGFR T790M and ectopically expressing an EGFR E746_A750del/EGFR T790M/EGFR L844V triple mutation in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR T790M EGFR L844V lung non-small cell carcinoma resistant Rociletinib Preclinical Actionable In a preclinical study, expression of an EGFR E746_A750del/EGFR T790M/EGFR L844V triple mutation conferred resistance to Rociletinib (CO-1686) in non-small cell lung cancer cells harboring EGFR E746_A750del and EGFR T790M in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR L718Q Advanced Solid Tumor sensitive Osimertinib Preclinical Actionable In a preclinical study, AZD9291 inhibited growth of transformed cells expressing an EGFR E746_A750del/EGFR L718Q double mutation in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR L718Q Advanced Solid Tumor resistant Rociletinib Preclinical Actionable In a preclinical study, transformed cells expressing an EGFR E746_A750del/EGFR L718Q double mutation demonstrated resistance to Rociletinib (CO-1686) in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR L718Q Advanced Solid Tumor sensitive Afatinib Preclinical Actionable In a preclinical study, Gilotrif (afatinib) inhibited growth of transformed cells expressing an EGFR E746_A750del/EGFR L718Q double mutation in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR T790M lung adenocarcinoma predicted - resistant Gefitinib Clinical Study Actionable In a retrospective analysis, 4 patients with lung adenocarcinoma harboring EGFR E746_A750del that had developed Iressa (gefitinib) resistance were found to have acquired EGFR T790M mutations (PMID: 18981003). 18981003
EGFR E746_A750del EGFR T790M lung adenocarcinoma predicted - resistant Gefitinib Case Reports/Case Series Actionable In a clinical case study, EGFR T790M was identified in a patient with lung adenocarcinoma harboring EGFR E746_A750del with resistance to Iressa (gefitinib) (PMID: 15737014). 15737014
EGFR E746_A750del EGFR T790M lung non-small cell carcinoma sensitive Rociletinib Preclinical - Cell culture Actionable In a preclinical study, Rociletinib (CO-1686) treatment reduced proliferation and EGFR pathway signaling in non-small cell lung cancer cells harboring EGFR E746_A750del and EGFR T790M in culture (PMID: 30322949). 30322949
EGFR E746_A750del EGFR T790M lung non-small cell carcinoma sensitive Naquotinib Preclinical - Cell culture Actionable In a preclinical study, Naquotinib (ASP8273) inhibited EGFR signaling and proliferation of non-small cell lung cancer cells harboring both EGFR E746_A750del and EGFR T790M in culture (PMID: 29467275). 29467275
EGFR E746_A750del EGFR T790M lung non-small cell carcinoma conflicting Afatinib Preclinical - Cell culture Actionable In a preclinical study, Gilotrif (afatinib) treatment did not reduce proliferation and EGFR pathway signaling in non-small cell lung cancer cells harboring EGFR E746_A750del and EGFR T790M in culture (PMID: 30322949). 30322949
EGFR E746_A750del EGFR T790M lung non-small cell carcinoma conflicting Afatinib Preclinical - Cell culture Actionable In a preclinical study, Gilotrif (afatinib) inhibited EGFR signaling and proliferation of non-small cell lung cancer cells harboring both EGFR E746_A750del and EGFR T790M in culture (PMID: 29467275). 29467275
EGFR E746_A750del EGFR T790M lung non-small cell carcinoma resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells harboring both EGFR E746_A750del and EGFR T790M were resistant to Tarceva (erlotinib) in culture (PMID: 29467275). 29467275
EGFR E746_A750del EGFR T790M lung non-small cell carcinoma sensitive Trametinib + WZ4002 Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with the combination of WZ4002 and Mekinist (trametinib) inhibited tumor growth, and resulted in increased ERK inhibition and reduced tumor rebound compared to WZ4002 alone in non-small cell lung cancer cell line xenograft models harboring both EGFR E746_A750del and EGFR T790M (PMID: 26036643). 26036643
EGFR E746_A750del EGFR T790M Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EGFR E746_A750del and T790M in culture (PMID: 27780853). 27780853
EGFR E746_A750del EGFR T790M lung adenocarcinoma predicted - resistant Erlotinib Clinical Study Actionable In a retrospective analysis, 3 of 4 patients with lung adenocarcinoma harboring EGFR E746_A750del, who were found to have acquired EGFR T790M upon disease progression on Iressa (gefitinib) therapy, had rapid disease progression in response to Tarceva (erlotinib) therapy (PMID: 18981003). 18981003
EGFR E746_A750del EGFR T790M lung non-small cell carcinoma sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, Tagrisso (osimertinib) inhibited EGFR signaling and proliferation of non-small cell lung cancer cells harboring both EGFR E746_A750del and EGFR T790M in culture (PMID: 29467275). 29467275
EGFR E746_A750del EGFR T790M lung non-small cell carcinoma sensitive Osimertinib Preclinical - Cell line xenograft Actionable In a preclinical study, Tagrisso (osimertinib) treatment reduced proliferation and EGFR pathway signaling in non-small cell lung cancer cells harboring EGFR E746_A750del and EGFR T790M in culture, and reduced tumor growth in cell line xenograft mouse models (PMID: 30322949). 30322949
EGFR E746_A750del MET amp lung non-small cell carcinoma sensitive Gefitinib + PHA-665752 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of PHA-665752 and Iressa (gefitinib) overcame Iressa (gefitinib) resistance in a cell line xenograft model of non-small cell lung cancer reported to harbor EGFR E746_A750del (PMID: 23542356), which has acquired resistance to Iressa (gefitinib) due to MET amplification and over expression, resulting in tumor growth inhibition (PMID: 24165158). 24165158 23542356
EGFR E746_A750del MET amp lung non-small cell carcinoma sensitive Gefitinib + NPS-1034 Preclinical - Cell line xenograft Actionable In a preclinical study, the addition of NPS-1034 to treatment with Iressa (gefitinib) overcame Iressa (gefitinib) resistance in a cell line xenograft model of non-small cell lung cancer reported to harbor EGFR E746_A750del (PMID: 23542356), which has acquired resistance to Iressa (gefitinib) due to MET amplification and over expression, resulting in tumor growth inhibition (PMID: 24165158). 24165158 23542356
EGFR E746_A750del MET amp lung adenocarcinoma sensitive Afatinib + Capmatinib Preclinical - Pdx Actionable In a preclinical study, treatment with Capmatinib (INC280) plus Gilotrif (afatinib) resulted in improved survival with no evidence of tumor 300 days post-transplantation in patient-derived xenograft (PDX) models derived from the brain metastasis of a lung adenocarcinoma patient with EGFR E746_A750del (referred to as K745_A750delinsK) and high level MET amplification (PMID: 28961841). 28961841
EGFR E746_A750del MET amp lung adenocarcinoma resistant Osimertinib Case Reports/Case Series Actionable In a clinical case study, a patient with metastatic lung adenocarcinoma harboring EGFR E746_A750del (referred to as K745_A750delinsK) and T790M demonstrated an initial response, but subsequent progression, of the brain metastasis following Tagrisso (osimertinib) treatment, and analysis of the brain metastasis showed loss of EGFR T790M as well as acquisition of high-level MET amplification, and resistance to Tagrisso (osimertinib) was recapitulated in a patient-derived xenograft (PDX) model (PMID: 28961841). 28961841
EGFR E746_A750del MET amp lung adenocarcinoma no benefit Afatinib Preclinical - Pdx Actionable In a preclinical study, treatment with Gilotrif (afatinib) did not demonstrate benefit in patient-derived xenograft (PDX) models derived from the brain metastasis of a lung adenocarcinoma patient with EGFR E746_A750del (referred to as K745_A750delinsK) and high level MET amplification, with all treated mice demonstrating progression (PMID: 28961841). 28961841
EGFR E746_A750del MET amp lung non-small cell carcinoma resistant Gefitinib Preclinical - Cell culture Actionable In a preclinical study, acquired amplification of MET conferred resistance to Iressa (gefitinib) in a non-small cell lung cancer cell line harboring EGFR E746_A750del in culture (PMID: 27612490). 27612490
EGFR E746_A750del MET amp lung non-small cell carcinoma resistant Rociletinib Preclinical - Cell line xenograft Actionable In a preclinical study, emergence of MET amplification was associated with resistance to Rociletinib (CO1686) in non-small cell lung cancer cell line xenograft models harboring EGFR E746_A750del (PMID: 27283993). 27283993
EGFR E746_A750del MET amp lung non-small cell carcinoma sensitive Crizotinib + Rociletinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Rociletinib (CO-1686) and Xalkori (crizotinib) overcame resistance to Rociletinib (CO-1686) in non-small cell lung cancer cell line harboring EGFR E746_A750del and MET amplification in culture (PMID: 27283993). 27283993
EGFR E746_A750del MET amp lung adenocarcinoma sensitive Capmatinib Preclinical - Pdx Actionable In a preclinical study, treatment with Capmatinib (INC280) resulted in improved survival in patient-derived xenograft (PDX) models derived from the brain metastasis of a lung adenocarcinoma patient with EGFR E746_A750del (referred to as K745_A750delinsK) and high level MET amplification (PMID: 28961841). 28961841
EGFR E746_A750del SMO amp lung non-small cell carcinoma no benefit Sonidegib Preclinical Actionable In a preclinical study, Odomzo (sonidegib) did not decrease viability or migration of non-small cell lung cancer cells harboring EGFR E746_A750del and amplification of SMO in culture (PMID: 26124204). 26124204
EGFR E746_A750del SMO amp lung non-small cell carcinoma resistant Gefitinib Preclinical Actionable In a preclinical study, amplification of SMO conferred acquired resistance to Iressa (gefitinib) in non-small cell lung cancer cells harboring EGFR E746_A750del in culture (PMID: 26124204). 26124204
EGFR E746_A750del SMO amp lung non-small cell carcinoma sensitive Gefitinib + Sonidegib Preclinical Actionable In a preclinical study, the combination of Odomzo (sonidegib) and Iressa (gefitinib) decreased viability and migration of non-small cell lung cancer (NSCLC) cells harboring an EGFR E746_A750del mutation and SMO amplification in culture and inhibited tumor growth in NSCLC xenograft models with EGFR E746_A750del and SMO amplification (PMID: 26124204). 26124204
EGFR E746_A750del SMO amp lung non-small cell carcinoma sensitive PHA-665752 + Sonidegib Preclinical Actionable In a preclinical study, the combination of Odomzo (sonidegib) and PHA-665752 decreased viability and migration of non-small cell lung cancer (NSCLC) cells harboring EGFR E746_A750del and SMO amplification in culture, and resulted in complete response in 100% (8/8) of NSCLC xenograft models with EGFR E746_A750del and SMO amplification (PMID: 26124204). 26124204
EGFR E746_A750del EGFR T790M EGFR L718Q Advanced Solid Tumor resistant Osimertinib Preclinical Actionable In a preclinical study, transformed cells expressing an EGFR E746_A750del/EGFR T790M/EGFR L718Q triple mutation demonstrated resistance to AZD9291 in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR T790M EGFR L718Q Advanced Solid Tumor resistant Rociletinib Preclinical Actionable In a preclinical study, transformed cells expressing an EGFR E746_A750del/EGFR T790M/EGFR L718Q triple mutation demonstrated resistance to Rociletinib (CO-1686) in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR T790M EGFR L718Q lung non-small cell carcinoma sensitive Osimertinib Preclinical Actionable In a preclinical study, AZD9291 inhibited growth of non-small cell lung cancer cells harboring EGFR E746_A750del and EGFR T790M and ectopically expressing an EGFR E746_A750del/EGFR T790M/EGFR L718Q triple mutation in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR T790M EGFR L718Q lung non-small cell carcinoma resistant Rociletinib Preclinical Actionable In a preclinical study, expression of an EGFR E746_A750del/EGFR T790M/EGFR L718Q triple mutation conferred resistance to Rociletinib (CO-1686) in non-small cell lung cancer cells harboring EGFR E746_A750del and EGFR T790M in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR C797S Advanced Solid Tumor sensitive Afatinib Preclinical Actionable In a preclinical study, Gilotrif (afatinib) inhibited growth of transformed cells expressing an EGFR E746_A750del/EGFR C797S double mutation in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR C797S Advanced Solid Tumor resistant Rociletinib Preclinical Actionable In a preclinical study, cells expressing an EGFR E746_A750del/EGFR C797S double mutation demonstrated resistance to Rociletinib (CO-1686) in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR C797S lung non-small cell carcinoma resistant WZ4002 Preclinical - Cell culture Actionable In a preclinical study, a non-small cell lung cancer cell line harboring EGFR E746_A750del and expressing EGFR E746_A750del/C797S demonstrated resistance to growth inhibition by WZ4002 in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR C797S lung non-small cell carcinoma sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, Gilotrif (afatinib) inhibited growth of a non-small cell lung cancer cell line harboring EGFR E746_A750del and expressing EGFR E746_A750del/C797S in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR C797S lung non-small cell carcinoma sensitive Gefitinib Preclinical - Cell culture Actionable In a preclinical study, Iressa (gefitinib) inhibited growth of a non-small cell lung cancer cell line harboring EGFR E746_A750del and expressing EGFR E746_A750del/C797S in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR C797S lung non-small cell carcinoma resistant Rociletinib Preclinical - Cell culture Actionable In a preclinical study, a non-small cell lung cancer cell line harboring EGFR DelE746_A750 and expressing EGFR DelE746_A750/C797S demonstrated resistance to growth inhibition by Rociletinib (CO1686) in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR C797S Advanced Solid Tumor resistant Osimertinib Preclinical Actionable In a preclinical study, transformed cells expressing an EGFR E746_A750del/EGFR C797S double mutation demonstrated resistance to AZD9291 in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR C797S lung non-small cell carcinoma resistant Osimertinib Preclinical - Cell culture Actionable In a preclinical study, a non-small cell lung cancer cell line harboring EGFR E746_A750del and expressing EGFR E746_A750del/C797S demonstrated resistance to growth inhibition by Tagrisso (osimertinib) in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR L792F Advanced Solid Tumor decreased response Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR E746_A750del and EGFR L792F demonstrated decreased sensitivity to Gilotrif (afatinib) in culture compared to cells expressing E746_A750del alone (PMID: 27913578). 27913578
EGFR exon 19 del NRAS Q61K lung non-small cell carcinoma resistant Osimertinib Preclinical Actionable In a preclinical study, non-small cell lung cancer cells harboring EGFR exon 19 deletion and NRAS Q61K were resistant to Tagrisso (osimertinib) in culture (PMID: 25870145). 25870145
EGFR exon 19 del NRAS Q61K lung non-small cell carcinoma sensitive Selumetinib Preclinical Actionable In a preclinical study, Selumetinib inhibited proliferation of non-small cell lung cancer cells harboring EGFR exon 19 deletion and NRAS Q61K in culture (PMID: 25870145). 25870145
EGFR exon 19 del NRAS Q61K lung non-small cell carcinoma resistant WZ4002 Preclinical Actionable In a preclinical study, non-small cell lung cancer cells harboring EGFR exon 19 deletion became resistant to WZ4002 after the emergence of NRAS Q61K in culture (PMID: 25870145). 25870145
EGFR exon 19 del MET amp lung adenocarcinoma predicted - sensitive Osimertinib + Savolitinib Case Reports/Case Series Actionable In a clinical case study, a patient with lung adenocarcinoma harboring an EGFR exon 19 deletion and MET amplification demonstrated a near complete response when treated with the combination of Savolitinib (AZD6094) and Tagrisso (osimertinib) obtained through a Phase I trial, however, after 36 weeks presented with progression (PMID: 27694386; NCT02143466). 27694386
EGFR exon 19 del MET amp lung adenocarcinoma resistant Erlotinib Case Reports/Case Series Actionable In a clinical case study, a patient with lung adenocarcinoma harboring an EGFR exon 19 deletion and MET amplification was resistant to Tarceva (erlotinib) (PMID: 27694386). 27694386
EGFR exon 19 del MET amp lung adenocarcinoma predicted - resistant Afatinib Case Reports/Case Series Actionable In a clinical case study, a patient with lung adenocarcinoma harboring an EGFR exon 19 deletion and MET amplification was resistant to Gilotrif (afatinib) (PMID: 27694386). 27694386
EGFR exon 19 del MET amp lung non-small cell carcinoma resistant Gefitinib Preclinical - Cell culture Actionable In a preclinical study, amplification of MET conferred resistance to Iressa (gefitinib) in non-small cell lung cancer cells harboring an EGFR exon 19 deletion mutation in culture (PMID: 17463250). 17463250
EGFR exon 19 del MET amp lung non-small cell carcinoma sensitive JNJ-61186372 Preclinical - Cell line xenograft Actionable In a preclinical study, JNJ-61186372 inhibited tumor growth in Tarceva (erlotinib)-resistant non-small cell lung cancer cell line xenograft models harboring an EGFR exon 19 deletion and MET amplification (PMID: 27216193). 27216193
EGFR exon 19 del MET amp MET D1228V lung adenocarcinoma predicted - resistant Osimertinib + Savolitinib Case Reports/Case Series Actionable In a clinical case study, a patient with lung adenocarcinoma harboring an EGFR exon 19 deletion and MET amplification demonstrated a near complete response when treated with the combination of Savolitinib (AZD6094) and Tagrisso (osimertinib) obtained through a Phase I trial, however, after 36 weeks presented with progression and MET D1228V was identified as an acquired mutation (PMID: 27694386; NCT02143466). 27694386
EGFR exon 19 del MET amp MET D1228V lung adenocarcinoma predicted - sensitive Cabozantinib + Erlotinib Case Reports/Case Series Actionable In a clinical case study, a patient with lung adenocarcinoma harboring an EGFR exon 19 deletion, MET amplification, and MET D1228V demonstrated a strong response to the combination of Tarceva (erlotinib) and Cometriq (Cabometyx, cabozantinib), resulting in reduced tumor size and continued clinical benefit 5 months after the start of therapy (PMID: 27694386). 27694386
EGFR exon 19 del EGFR K754E lung adenocarcinoma decreased response Erlotinib Preclinical - Cell culture Actionable In a preclinical study, expression of EGFR K754E in lung adenocarcinoma cells harboring EGFR exon 19 deletion mutations led to decreased response to Tarceva (erlotinib) compared to control cells in culture (PMID: 27478040). 27478040
EGFR exon 19 del ERBB2 wild-type Advanced Solid Tumor sensitive Osimertinib Preclinical Actionable In a preclinical study, transgenic mouse models with ERBB2 (HER2)-wild-type cells expressing EGFR exon 19 deletion demonstrated tumor growth inhibition and an improved progression-free survival when treated with Tagrisso (osimertinib) compared to treatment with Tarceva (erlotinib) (PMID: 29298799). 29298799
EGFR exon 19 del lung non-squamous non-small cell carcinoma sensitive Gefitinib Guideline Actionable Iressa (gefitinib) is included in guidelines as first-line therapy for advanced, recurrent, or metastatic nonsquamous non-small cell lung carcinoma patients harboring sensitizing EGFR mutations, including exon 19 deletion and L858R (NCCN.org). detail...
EGFR exon 19 del lung non-squamous non-small cell carcinoma sensitive Afatinib Guideline Actionable Gilotrif (afatinib) is included in guidelines as first-line, but not subsequent therapy for metastatic nonsquamous non-small cell lung carcinoma patients harboring sensitizing EGFR mutations, including exon 19 deletion and L858R (NCCN.org). detail...
EGFR exon 19 del Advanced Solid Tumor sensitive BGB-283 Preclinical - Cell culture Actionable In a preclinical study, BGB-283 inhibited proliferation of transformed cells over expressing EGFR exon 19 deletion mutation in culture (PMID: 26208524). 26208524
EGFR exon 19 del lung non-small cell carcinoma predicted - sensitive Erlotinib + GLPG0634 Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung carcinoma cells harboring EGFR exon 19 deletion in culture that had, over time, acquired resistance to Tarceva (erlotinib) showed decreased drug resistance when treatment was combined with Filgotinib (GLPG0634), demonstrating reduced expression of Osmr and phosphorylated-Stat3, and decreased cell viability (PMID: 28729401). 28729401
EGFR exon 19 del lung adenocarcinoma sensitive Gefitinib + Golvatinib Preclinical - Cell line xenograft Actionable In a preclinical study, addition of Golvatinib (E7050) overcame Hgf-induced Iressa (gefitinib)-resistance in lung adenocarcinoma cell lines harboring EGFR exon 19 deletions in culture and in cell line xenograft models (PMID: 22789825). 22789825
EGFR exon 19 del lung non-small cell carcinoma sensitive Gefitinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial that supported FDA approval, Iressa (gefitinib) treatment resulted in an objective response rate of 71.2% (94/132) compared to 47.3% (61/129) with Paraplatin (carboplatin) plus Taxol (paclitaxel) and prolonged progression-free survival (HR=0.48) in non-small cell lung cancer patients harboring EGFR activating mutations, including EGFR exon 19 deletions (PMID: 19692680, NCT00322452). detail... detail... 19692680
EGFR exon 19 del lung non-small cell carcinoma sensitive Gefitinib Clinical Study - Cohort Actionable In a clinical study, a comparison of the clinical outcomes of non-small cell lung cancer patients harboring either EGFR exon 19 deletion or L858R demonstrated similar responses to treatment with Iressa (gefitinib) or Tarceva (erlotinib), with overall response rates of 76.9% with Iressa (gefitinib) and 74.4% with Tarceva (erlotinib) (PMID: 24736073). 24736073
EGFR exon 19 del