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
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).
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 cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Oct 2018).
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, Jun 2018).
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.
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.
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).
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).
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.
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).
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, Aug 2018).
R831C missense no effect - predicted EGFR R831C lies within the cytoplasmic 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.
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_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).
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).
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 not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Aug 2018).
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, Aug 2018).
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.
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, Jun 2018).
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).
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), but has not been biochemically characterized and therefore its effect on Egfr protein is unknown (PubMed, Jul 2018).
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).
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.
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, Jun 2018).
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.
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.
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, Jul 2018).
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).
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).
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, Aug 2018).
P546S missense unknown EGFR P546S lies within the extracellular domain of the Egfr protein (UniProt.org). P546S 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 (PubMed, Oct 2018).
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.
G721D missense unknown EGFR G721D lies within the protein kinase domain of the Egfr protein (UniProt.org). G721D is predicted to confer a gain of function on Egfr by computer modeling (PMID: 24817905), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Oct 2018).
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).
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).
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.
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).
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.
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, Aug 2018).
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.
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.
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, Jun 2018).
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).
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, Jun 2018).
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, Aug 2018).
L838M missense no effect - predicted EGFR L838M lies within the cytoplasmic 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.
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).
V292L missense unknown EGFR V292L lies within the extracellular domain 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, Sep 2018).
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).
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).
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, Aug 2018).
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).
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).
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
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, Jul 2018).
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
amp none no effect EGFR amp indicates an increased number of copies of the EGFR gene. However, the mechanism causing the increase is unspecified.
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.
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.
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, Aug 2018).
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 cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Oct 2018).
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).
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, Aug 2018).
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.
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), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Jul 2018).
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, Jun 2018).
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.
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, Aug 2018).
R521K missense unknown EGFR R521K (also reported as R497K) lies within the repeat region of the Egfr protein (UniProt.org). R521K has been demonstrated to result in decreased Egfr response in cultured cells (PMID: 7937865) and in one of two cell lines, R521K 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 (PubMed, Oct 2018)..
S784F missense unknown EGFR S784F lies within the protein kinase domain of the Egfr protein (UniProt.org). S784F has been demonstrated to result in constitutive Egfr phosphorylation, activation of downstream signaling, and transformation of cultured cells in one study (PMID: 19147750), however, in another study S784F induced cell proliferation and viability similar to wild-type Egfr in culture (PMID: 29533785) and therefore, its effect on Egfr protein function is unknown.
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).
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
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, Aug 2018).
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).
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, Jul 2018).
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 cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Oct 2018).
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).
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, Sep 2018).
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 cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Oct 2018).
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).
P622S missense unknown EGFR P622S lies within the extracellular domain of the Egfr protein (UniProt.org). P622S has not been characterized in the scientific literature and therefore, its effect on Egfr protein function is unknown (PubMed, Jun 2018).
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).
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, Aug 2018).
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, Aug 2018).
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).
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, Aug 2018).
F795L missense unknown EGFR F795L lies within the protein kinase domain of the Egfr protein (UniProt.org). F795L has not been characterized in the scientific literature and therefore, its effect on Egfr protein function is unknown (PubMed, Jun 2018).
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, Aug 2018).
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).
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, Aug 2018).
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, Aug 2018).
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).
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).
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 R841K 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).
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
T854A missense unknown EGFR T854A lies within the protein kinase domain of the Egfr protein (UniProt.org). T854A has been associated with acquired resistance to Egfr tyrosine kinase inhibitor (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 (PubMed, Oct 2018). Y
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).
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 cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Oct 2018).
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, Jul 2018).
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).
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.
C797G missense unknown 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), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Oct 2018). Y
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.
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.
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
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, Sep 2018).
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.
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, Jul 2018).
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 cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Oct 2018).
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.
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).
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 cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Oct 2018).
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, Aug 2018).
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, Sep 2018).
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.
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).
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.
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.
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).
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, Aug 2018).
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, Aug 2018).
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.
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, Jun 2018). Y
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, Aug 2018).
EGFR - SEPT14 fusion gain of function EGFR-SEPT14 results from the fusion of EGFR and SEPT14, demonstrating increased cell proliferation, self-renewal, migration, and activated STAT3 signaling in cell culture (PMID: 23917401). EGFR-SEPT14 has been identified in glioblastoma (PMID: 26762204, PMID: 23917401).
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, it's effect on Egfr protein function is unknown (PubMed, Jun 2018). Y
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, Sep 2018).
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).
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).
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.
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 not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Aug 2018).
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).
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).
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
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, Sep 2018).
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, Sep 2018).
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, Jun 2018). Y
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
del deletion loss of function EGFR del indicates a deletion of the EGFR gene.
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).
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, Aug 2018).
mutant unknown unknown EGFR mut indicates an unspecified mutation in the EGFR gene.
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).
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, Jun 2018).
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, Aug 2018).
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).
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).
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.
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).
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, Jun 2018).
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), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Jun 2018).
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.
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, Aug 2018).
L90F missense unknown EGFR L90F lies within the extracellular domain of the Egfr protein (UniProt.org). L90F has not been characterized in the scientific literature and therefore, its effect on Egfr protein function is unknown (PubMed, Jun 2018).
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).
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).
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, Aug 2018).
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).
V765L missense unknown EGFR V765L lies within the protein kinase domain of the Egfr protein between (UniProt.org). V765L has not been characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Sep 2018).
N826S missense unknown EGFR N826S lies within the protein kinase domain of the Egfr protein (UniProt.org). N826S resulted in constitutive Egfr phosphorylation, activation of downstream Erk, Stat5, and Akt signaling, transformation of cultured cells, and was associated with drug resistance in one study (PMID: 19147750), however, in another study N826S demonstrated 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
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, Jul 2018).
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).
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.
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).
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, Aug 2018).
L858M missense unknown EGFR L858M lies within the protein kinase domain of the Egfr protein (UniProt.org). L858M has been identified in the scientific literature (PMID: 28088511) but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Sep 2018).
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, Jul 2018).
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
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 cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Oct 2018).
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).
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).
P699S missense unknown EGFR P699S lies within 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 cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Oct 2018).
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 bot been biochemically characterized and therefore its effect on Egfr protein function is unknown.
D770_N771insNPG insertion gain of function EGFR D770_N771insNPG 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_N771insNPG results in increased Egfr kinase activity and is transforming in culture (PMID: 24353160).
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).
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.
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).
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).
L692P missense unknown EGFR L692P lies within the protein kinase domain 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, Jun 2018).
wild-type none no effect Wild-type EGFR indicates that no mutation has been detected within the EGFR gene.
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.
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).
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, Jun 2018).
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.
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, Jul 2018).
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).
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).
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).
S492R missense unknown EGFR S492R lies within the extracellular domain of the Egfr protein (UniProt.org). S492R increased cell proliferation and viability in one of two cell lines in culture (PMID: 29533785), and confers resistance to Erbitux (cetuximab) in cell culture (PMID: 26059438), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Sep 2018). Y
Y1016H missense unknown EGFR Y1016H lies within a site in the Egfr protein important for interaction with PIK3C2B (UniProt.org). Y1016H has not been characterized in the scientific literature and therefore, its effect on Egfr protein function is unknown (PubMed, Jun 2018).
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).
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).
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, Sep 2018).
EGFR - FGFR1 fusion unknown EGFR-FGFR1 results form 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, its effect on protein function is unknown (PubMed, Oct 2018).
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).
A864T missense unknown EGFR A864T lies within the protein kinase domain of the Egfr protein (UniProt.org). A864T resulted in ligand-independent Egfr autophosphorylation and activation of Akt and Erk signaling in cell culture in one study (PMID: 19147750), but induced similar cell proliferation and 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.
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).
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).
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.
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, Aug 2018).
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).
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, Jun 2018).
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, Sep 2018).
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, Aug 2018).
G873E missense unknown EGFR G873E lies within the protein kinase domain of the Egfr protein (UniProt.org). G873E has been identified in the scientific literature (PMID: 21030498, PMID: 23800712), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Aug 2018).
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, Aug 2018).
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).
exon19 unknown unknown EGFR exon 19 indicates an unspecified mutation has occurred in exon 19 of the EGFR gene.
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, Aug 2018).
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 cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Oct 2018).
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).
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).
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, Aug 2018).
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.
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, Sep 2018).
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.
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.
Q432R missense unknown EGFR Q432R lies within the extracellular domain 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, Sep 2018).
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).
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.
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
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).
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.
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, Aug 2018).
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.
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, Jun 2018). Y
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, Jun 2018).
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, Sep 2017).
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).
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, Oct 2018).
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).
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, Aug 2018).
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.
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, Sep 2018).
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, Sep 2018).
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).
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, Jul 2018).
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).
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, Jun 2018). Y
G719X missense gain of function - predicted 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).
P848L missense unknown EGFR P848L lies within the protein kinase domain of the Egfr protein (UniProt.org). P848L resulted in lower Egfr autophosphorylation levels compared to activating mutation L858R (PMID: 17877814), but results in increased cell proliferation and cell viability as compared to wild-type Egfr in one of two cell lines in another study (PMID: 29533785) and therefore, its effect on Egfr protein function is unknown.
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, Aug 2018).
A750P missense unknown EGFR A750P lies within the protein kinase domain of the Egfr protein (UniProt.org). A750P resulted in ligand-independent phosphorylation of Egfr in cell culture and promoted tumor formation in xenograft models in one study (PMID: 19625781), but induced 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.
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, Jun 2018).
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, Sep 2018).
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).
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, Aug 2018).
A859T missense unknown EGFR A859T lies within the protein kinase domain of the Egfr protein (UniProt.org). A859T did not result in increased Egfr autophosphorylation and was not able to induce phosphorylation of Akt in culture (PMID: 17877814), however in another study, A859T demonstrated increased transformation ability in one of two different cell lines (PMID: 29533785) and therefore, its effect on Egfr protein function is unknown.
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, Jun 2018). Y
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).
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, Aug 2018).
D761Y missense unknown EGFR D761Y lies within the protein kinase domain of the Egfr protein (UniProt.org). D761Y has been demonstrated to decrease sensitivity to Egfr tyrosine kinase inhibitors in culture (PMID: 17085664), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Oct 2018). Y
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).
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
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).
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).
V742A missense unknown EGFR V742A lies within the protein kinase domain of the Egfr protein (UniProt.org). V742A resulted in growth factor-independent cell proliferation in one study (PMID: 19147750), but induced both increased and decreased cell proliferation as compared to wild-type Egfr in another study (PMID: 29533785) and therefore, its effect on Egfr protein function is unknown (PubMed, Oct 2018).
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.
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, Aug 2018).
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.
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).
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), but in another study, E868G induced similar cell proliferation and cell viability levels as wild-type Egfr (PMID: 29533785) and therefore, its effect on Egfr protein function is unknown.
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).
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, Aug 2018).
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, Sep 2018).
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.
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, Aug 2018).
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, Jul 2018).
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 cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Oct 2018).
P753S missense unknown EGFR P753S lies within the protein kinase domain of the Egfr protein (UniProt.org). P753S is predicted to be an activating, oncogenic mutation based on SIFT analysis (PMID: 18006781), but has bot been biochemically characterized and therefore its effect on Egfr protein function is unknown.
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.
V765G missense unknown EGFR V765G lies within the protein kinase domain of the Egfr protein (UniProt.org). V765G results in 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, Oct 2018).
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.
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, Aug 2018).
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, Jul 2018).
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.
positive unknown unknown EGFR positive indicates the presence of the EGFR gene, mRNA, and/or protein.
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).
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 (PubMed, Oct 2018).
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.
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.
negative unknown loss of function EGFR negative indicates a lack of the EGFR gene, mRNA, and/or protein.
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.
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.
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, Jun 2018).
loss unknown loss of function EGFR loss indicates loss of the EGFR gene, mRNA, and protein.
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, Sep 2018).
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, Jul 2018).
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, Aug 2018).
exon21 unknown unknown EGFR exon 21 indicates an unspecified mutation has occurred in exon 21 of the EGFR gene.
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, Oct 2018). Y
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).
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.
V592I missense no effect - predicted 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 in one study (PMID: 29533785) and therefore, is predicted to have no effect on Egfr protein function.
C797S missense unknown EGFR C797S lies within the ATP-binding pocket in the protein kinase domain of the Egfr protein (PMID: 25964297). C797S has been demonstrated to confer resistance to third-generation EGFR inhibitors (PMID: 25964297, PMID: 25948633, PMID: 29410323), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Jun 2018). Y
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).
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, Aug 2018).
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 cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Oct 2018).
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
L747P missense unknown EGFR L747P lies within the protein kinase domain of the Egfr protein (UniProt.org). L747P has been identified in patients insensitive to Egfr TKI (PMID: 26339441, PMID: 21531810), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Oct 2018). Y
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, Jun 2018). Y
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).
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) but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Jul 2018).
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.
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, Aug 2018).
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.
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).
G588S missense unknown EGFR G588S lies within the extracellular domain 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, Sep 2018).
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.
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), but in another study, G735S induced 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.
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.
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).
dec exp none no effect EGFR dec exp indicates decreased expression of the Egfr protein. However, the mechanism causing the decreased expression is unspecified.
Q105H missense no effect - predicted EGFR Q105H lies within the extracellular domain of the Egfr protein (UniProt.org). Q105H 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_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).
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, Jun 2018).
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, Jun 2018).
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).
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).
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.
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, Jun 2018). 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).
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, Aug 2018).
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).
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).
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, Jun 2018).
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 cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Oct 2018).
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, Sep 2018).
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), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Jun 2018).
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.
P794L missense unknown EGFR P794L lies within the cytoplasmic 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, May 2018). Y
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, Oct 2018).
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).
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, its effect on fusion protein function is unknown (PubMed, Aug 2018).
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).
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, Aug 2018).
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.
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.
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).
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.
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
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
A763V missense unknown EGFR A763V lies within the protein kinase domain of the Egfr protein (UniProt.org). A763V is associated with a lack of response to an Egfr kinase inhibitor (PMID: 15897572), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Oct 2018). Y
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).
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, Aug 2018).
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, Jul 2018).
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).
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), and promotes tumor formation in mouse models (PMID: 16187797).
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).
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, Sep 2018).
exon20 unknown unknown EGFR exon 20 indicates an unspecified mutation has occurred in exon 20 of the EGFR gene.
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).
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).
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.
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), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Aug 2018).
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, Jun 2018).
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, Jun 2018).
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.
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, Sep 2018). Y
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, Jun 2018).
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).
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
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, Jun 2018).
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 cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Oct 2018).
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 cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Egfr protein function is unknown (PubMed, Oct 2018).
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).
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).
E884K missense unknown EGFR E884K lies within the protein kinase domain of the Egfr protein (UniProt.org). E884K results in constitutive phosphorylation of Egfr and 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), however in another study, E884K resulted in similar cell proliferation and 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.
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, and frequently occurrs as secondary somatic mutation that confers resistance to reversible tyrosine kinase inhibitors (PMID: 17671201, PMID: 18227510, PMID: 20026433). Y
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).
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).
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).
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).
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).
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).
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
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, Oct 2018).
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).
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, Jul 2018).
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).
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.
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.
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, Aug 2018).
Molecular Profile Protein Effect Treatment Approaches
EGFR E746K gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR T263I unknown
EGFR V786M unknown
EGFR D855G loss of function - predicted
EGFR Q701* loss of function - predicted
EGFR V769_D770insGVV gain of function - predicted
EGFR D770_N771insNPY gain of function - predicted
EGFR R252P gain of function - predicted
EGFR S768I gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR G721C unknown
EGFR R831C no effect - predicted
EGFR I491M gain of function
EGFR E746_T751delinsL gain of function - predicted
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 A839V unknown
EGFR D761G unknown
EGFR R252C no effect - predicted
EGFR L814P unknown
EGFR L858Q unknown
EGFR T847I unknown
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 K737E no effect - predicted
EGFR P281T unknown
EGFR P596L gain of function - predicted Afatinib Osimertinib
EGFR D191N no effect - predicted
EGFR S720F unknown
EGFR D770_N771insGL gain of function - predicted
EGFR D770_N771insGF gain of function - predicted
EGFR K754H unknown
EGFR P546S unknown
EGFR Q1164R no effect - predicted
EGFR G721D 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 L688P loss of function
EGFR P373Q no effect - predicted
EGFR A767_V769dup gain of function
EGFR E690K no effect - predicted
EGFR D1014V unknown
EGFR E114K no effect - predicted
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 S752I unknown
EGFR L747_T751del EGFR S752I
EGFR G598V gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR L792P unknown
EGFR G696_P1033dup gain of function
EGFR amp EGFR G696_P1033dup
EGFR H850D unknown
EGFR L838M no effect - predicted
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 E746_S752del EGFR T790M EGFR P794L
EGFR V292L 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 T725M gain of function
EGFR K757R unknown
EGFR G719A EGFR L861Q EGFR T790M
EGFR amp EGFR G719A
EGFR G719A EGFR T790M
EGFR G719A EGFR L861Q
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 A289V gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR N771_H773dup gain of function
EGFR P596R unknown
EGFR G465E EGFR G465R
EGFR G465E gain of function
EGFR amp EGFR over exp
EGFR amp FGFR1 amp
EGFR amp ERBB2 pos
EGFR amp EGFR E746_A750del
PDGFRA amp EGFR amp
EGFR amp no effect EGFR Antibody EGFR Inhibitor (Pan) HER inhibitor (Pan)
EGFR amp EGFR wild-type EGFR act mut
EGFR amp EGFR S492R BRAF V600E
EGFR act mut EGFR amp
EGFR amp ERBB2 amp
EGFR amp MET amp
EGFR amp EGFR act mut PTEN R308C
BRAF V600E EGFR amp
EGFR amp PTEN loss
EGFR amp ERBB2 over exp
EML4-ALK EGFR amp
EGFR amp EGFR S492R
EGFR amp FGFR1 amp KRAS G13C
EGFR D1072E no effect - predicted
EGFR act mut EGFR C797S EGFR T790M
EGFR C797S EGFR act mut
EGFR act mut MET amp
EGFR act mut EGFR T790M
EGFR act mut EGFR A289T PTEN I253N PTEN N69D
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 G721S unknown
EGFR T354M unknown
EGFR D770_N771insSVD gain of function - predicted
EGFR A216T unknown
EGFR S220P no effect - predicted
EGFR S752P unknown
EGFR N700D unknown
EGFR G573* loss of function - predicted
EGFR A871V unknown
EGFR R521K FGFR2 M186T KDR Q472H KDR V297I RET M1009T
EGFR R521K unknown
EGFR S784F 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 L747S gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR L858R EGFR L747S
EGFR E734K 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 V765A unknown
EGFR H47Y unknown
EGFR I740_P741insIHR gain of function - predicted
EGFR R889G unknown
EGFR P589L unknown
EGFR L861R gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR P622S unknown
EGFR D770_N771insGV gain of function - predicted
EGFR A755G unknown
EGFR A698T unknown
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 F254I unknown
EGFR F795L unknown
EGFR G857R unknown
EGFR L861Q gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR G719S EGFR L861Q
EGFR R1052I unknown
EGFR G721A unknown
EGFR D770_P772dup 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 R841K unknown
EGFR S464L gain of function
EGFR G465R EGFR S464L
EGFR exon 19 del EGFR T854A
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 K754E gain of function
EGFR exon 19 del EGFR K754E
EGFR V292M unknown
EGFR S720C 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 E45Q no effect - predicted
EGFR C797G unknown
EGFR M766_A767insAA gain of function - predicted
EGFR T625A no effect - predicted
EGFR A767T gain of function - predicted
EGFR G312W unknown
EGFR E513D no effect - predicted
EGFR P741L unknown
EGFR L62R unknown
EGFR L38V no effect - predicted
EGFR N771dup gain of function - predicted
EGFR M178I unknown
EGFR H773R unknown
EGFR L833F unknown
EGFR R222C gain of function - predicted Afatinib Osimertinib
EGFR E709_T710delinsD EGFR L792F
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 E734Q gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR P794S no effect - predicted
EGFR P772_H773insPHA gain of function - predicted
EGFR E709V unknown
EGFR K806A unknown
EGFR over exp PIK3CA E542K
EGFR over exp FGFR1 over exp
EGFR over exp + ERBB2 wild type
EGFR over exp FGFR1 amp
EGFR over exp KRAS wild-type
EGFR over exp FGFR2 amp
BRAF D594N BRAF G466A EGFR over exp MET over exp
BRAF V600E EGFR over exp
EGFR over exp no effect
EGFR over exp ERBB2 dec exp
EGFR V851I unknown
EGFR G779F unknown
EGFR-SEPT14 gain of function
EGFR L792H unknown
EGFR C797S EGFR L792H EGFR L858R
EGFR S1153I 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 A750P EGFR L747_E749del
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 V769M gain of function - predicted
EGFR A864V unknown
EGFR H773dup gain of function
EGFR-PPARGC1A gain of function
EGFR S645C gain of function
EGFR exon 19 del EGFR S645C
EGFR P1202Q unknown
EGFR E967A unknown
EGFR E865K unknown
EGFR E804G EGFR P699L
EGFR P699L loss of function - predicted
EGFR del loss of function
EGFR V769_D770insERG gain of function - predicted
EGFR K714R unknown
EGFR mut MET amp
EGFR mut TP53 mut
EGFR mut TP53 exon 8
EGFR mutant unknown
EGFR mut TP53 inact mut
EGFR T790M EGFR mut
EGFR mutant FGFR1 wild-type
EGFR V769_D770insGSV gain of function - predicted
EGFR L730F unknown
EGFR E868V 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 T790M
EGFR L747_P753delinsS EML4-ALK
EGFR L747_P753delinsS + EGFR T790M
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 C797S + EGFR L747_P753delinsS + EGFR T790M
EGFR D1009N no effect - predicted
EGFR L838V gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR V738G unknown
EGFR S784P unknown
EGFR R451C loss of function - predicted
EGFR E758G unknown
EGFR L90F unknown
EGFR D761_E762insEAFQ gain of function - predicted
EGR G735A unknown
EGFR I706T unknown
EGFR R108K gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR V765L unknown
EGFR N826S unknown
EGFR P733L 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 K708M no effect - predicted
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 H850Y unknown
EGFR L858M unknown
EGFR R748I unknown
EGFR G465R gain of function
BRAF V600E EGFR G465R
EGFR S768T unknown
EGFR D770_N771insGD gain of function - predicted
EGFR E746_P753delinsVS gain of function - predicted
EGFR P699S unknown
EGFR T751I unknown
EGFR C797S EGFR D770_N771insNPG EGFR T790M
EGFR D770_N771insNPG gain of function
EGFR D770_N771insNPG EGFR T790M
EGFR P772_H773dup gain of function - predicted
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 H773_V774insQ gain of function - predicted
EGFR K745M loss of function
EGFR L692P unknown
EGFR wild-type no effect
BRAF G466V EGFR wild-type
EGFR wild-type MET wild-type
ALK wild-type EGFR wild-type
EGFR wild-type MET over exp
EGFR wild-type STK11 wild-type TP53 mut
EGFR S116F no effect - predicted
EGFR G810S gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR L703P 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 R776S unknown
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 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 G796S gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR S492R unknown Afatinib Osimertinib
EGFR Y1016H 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 T34_A289del gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR R803W unknown
EGFR-FGFR1 unknown
EGFR-FGFR1 EGFR L858R
EGFR K739_I744dup gain of function
EGFR A864T unknown
EGFR H773_V774insAH gain of function - predicted
EGFR K721M loss of function
EGFR I475V no effect - predicted
EGFR F856_G857insYIV unknown
EGFR N771delinsFH gain of function - predicted
EGFR T710del unknown
EGFR L861F unknown
EGFR F712Y unknown
EGFR G873E unknown
EGFR D770N unknown
EGFR D770_N771insG gain of function - predicted
EGFR exon19 unknown
EGFR I744M unknown
EGFR L718P unknown
EGFR P772_H773insPNP gain of function - predicted
EGFR H870R gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR A1118T unknown
EGFR F712L no effect - predicted
EGFR V834M unknown
EGFR T751fs loss of function - predicted
EGFR K745R loss of function - predicted
EGFR Q432R 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 G983R gain of function - predicted
EGFR Y764_V765insHH gain of function - predicted Afatinib Naquotinib Osimertinib
EGFR N771_P772insRH gain of function - predicted
EGFR P772R gain of function - predicted
EGFR A702T unknown
EGFR L747* loss of function - predicted
EGFR A750V unknown
EGFR S921R unknown
EGFR G779S 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 A289T unknown
EGFR E709X unknown
EGFR G874S unknown
EGFR L633F no effect - predicted
EGFR P959fs unknown
EGFR V802I unknown
EGFR exon 19 del EGFR T790M NRAS Q61K
EGFR exon 19 del TP53 wild-type
BRAF V600E EGFR exon 19 del MET amp
EGFR exon 19 del KRAS G12S
EGFR exon 19 del EGFR T790M MET amp
EGFR exon 19 del EGFR T790M
EGFR exon 19 del EGFR T790M KRAS amp
EGFR exon 19 del MET amp MET D1228V
EGFR exon 19 del NRAS Q61K
EGFR exon 19 del KRAS amp
EGFR exon 19 del NRAS G12R
EGFR exon 19 del NRAS amp
EGFR exon 19 del NRAS E63K
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 EGFR exon 19 ins
EGFR exon 19 del MET act mut
EGFR exon 19 del MET amp
EGFR C797S EGFR exon 19 del EGFR T790M
EGFR exon 19 del ERBB2 wild-type
EGFR C797S EGFR exon 19 del
EGFR exon 19 del NRAS G12V
EGFR S752Y unknown
EGFR S768_D770dup gain of function - predicted
EGFR L858R EGFR V765_M766delinsHH
EGFR V765_M766delinsHH unknown
EGFR G719X gain of function - predicted EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan) Neratinib
EGFR P848L unknown
EGFR E709H unknown
EGFR A750P unknown
EGFR K806E unknown
EGFR E746_T751delinsA unknown
EGFR D770_N771insGT gain of function - predicted
EGFR A767V unknown
EGFR A859T unknown
EGFR L792F unknown
EGFR E746_A750del EGFR L792F
EGFR L792F EGFR L858R
EGFR D770_N771insAPW gain of function - predicted
EGFR G810D unknown
EGFR D761Y unknown
EGFR D761Y EGFR L858R EGFR Inhibitor 3rd gen
EGFR D770_N771insY gain of function - predicted
EGFR V769L gain of function - predicted
EGFR K745_E746insTPVAIK gain of function
EGFR R776G gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR V742A unknown
EGFR R108G gain of function - predicted
EGFR A120P unknown
EGFR S198R no effect - predicted
EGFR V769_D770insMASVD gain of function - predicted
EGFR E868G unknown
EGFR I853T loss of function
EGFR C775Y unknown
EGFR R831L unknown
EGFR E282K no effect - predicted
EGFR F712S unknown
EGFR T783A unknown
EGFR N444S unknown
EGFR P753S unknown
EGFR P1059R no effect - predicted
EGFR V765G unknown
EGFR D612N no effect - predicted
EGFR G857E unknown
EGFR P733S unknown
EGFR P272L loss of function - predicted
KRAS mut EGFR pos
EGFR pos KRAS wild-type
EGFR positive unknown
EGFR pos KRAS mut
EGFR pos ERBB2 pos
EGFR T263P gain of function
EGFR D256Y unknown
EGFR S229C gain of function - predicted
EGFR V774L no effect - predicted
EGFR negative loss of function
EGFR neg FGFR1 over exp
EGFR R98Q no effect - predicted
EGFR P596S gain of function - predicted
EGFR L798H unknown
EGFR loss loss of function
EGFR loss KRAS G12S
EGFR G719D unknown EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan) Neratinib
EGFR R832H unknown
EGFR G873Q unknown
EGFR exon21 unknown
EGFR H773L unknown
EGFR A871G gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR Q787R gain of function - predicted
EGFR V592I no effect - predicted
EGFR D770delinsGY EGFR C797S
EGFR C797S EGFR L858R EGFR T790M
EGFR E746_A750del EGFR T790M EGFR C797S
EGFR L858R EGFR C797S
EGFR E746_A750del EGFR C797S
EGFR C797S unknown
EGFR C797S EGFR T790M
EGFR R776H gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR H773Y unknown
EGFR H835L unknown
EGFR L833V EGFR H835L
EGFR D770delinsGY gain of function Dacomitinib
EGFR D770delinsGY EGFR T790M
EGFR L747P unknown
EGFR S306L unknown
EGFR L704N loss of function
EGFR S720P unknown
EGFR G42D no effect - predicted
EGFR G810A unknown
EGFR G598A no effect - predicted
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 G588S unknown
EGFR H304Y gain of function - predicted
EGFR G735S unknown
EGFR W731* loss of function - predicted
EGFR D761N gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR dec exp KRAS mut
EGFR dec exp KRAS wild-type
EGFR dec exp no effect
EGFR Q105H no effect - predicted
EGFR E746_A750del MET amp
EGFR E746_A750del FGFR3-TACC3
EGFR E746_A750del EGFR T790M EGFR L844V
EGFR E746_A750del EGFR L718Q
EGFR E746_A750del EML4-ALK
EGFR E746_A750del EGFR T790M
EGFR E746_A750del EGFR T790M EGFR Q791R
EGFR E746_A750del gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR E746_A750del EGFR L844V
EGFR E746_A750del SMO amp
EGFR E746_A750del EGFR T790M EGFR L718Q
EGFR K860I unknown
EGFR S784Y unknown
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 exon 20 ins gain of function
EGFR G719fs loss of function - predicted
EGFR L703I unknown
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 I821T unknown
EGFR L792_M793insHIV gain of function - predicted
EGFR G724S gain of function Cetuximab
EGFR G696E unknown
EGFR V148M unknown
EGFR L858K unknown
EGFR V774M unknown
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 P794L unknown
EGFR A702S unknown
EGFR V769_D770insASV gain of function - predicted
EGFR-PURB unknown Erlotinib
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 H870Y unknown
EGFR L1087P no effect - predicted
EGFR L747_A750delinsP FGFR3-TACC3
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 V851A loss of function
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 A871T no effect - predicted
EGFR L718Q no effect - predicted
EGFR L858R EGFR L718Q EGFR T790M
EGFR L858R EGFR L718Q
EGFR A763V unknown
EGFR V769_N771dup gain of function - predicted
EGFR D994Y unknown
EGFR S752F 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 L858R KRAS G12R
EGFR L858R MET amp
EGFR I941R EGFR L858R EGFR T790M
EGFR L858R EGFR T790M MET amp
EGFR L858R EGFR T790M PIK3CA G118D
EGFR L858R EGFR T790M NRAS Q61K
EGFR L858R EGFR L844V EGFR T790M
ALK amp EML4-ALK EGFR L858R
EGFR L858R EGFR T790M MET amp MET D1231Y
EGFR L858R EGFR T790M MET amp MET D1228H D1228N D1231Y Y1230H
EGFR L858R EGFR Q791R EGFR T790M
EGFR L858R KRAS G12D
EGFR L858R EGFR L844V
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 KRAS G12V
EGFR L858R EGFR T790M EGFR Inhibitor 3rd gen
EGFR L858R FGFR3-TACC3
EGFR L858R EML4-ALK
EGFR L858R EGFR E884K
EGFR D770_N771insMATP gain of function - predicted
EGFR V834L unknown
EGFR exon20 unknown
EGFR H773_V774dup gain of function - predicted
EGFR E804G gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR T363I gain of function - predicted
EGFR R675Q unknown
EGFR T854S unknown
EGFR Y125C unknown
EGFR G863D no effect - predicted
EGFR Q791R unknown
EGFR A613T unknown
EGFR L747_A755delinsSRD gain of function - predicted
EGFR K467T gain of function
EGFR V843I gain of function
EGFR V765M unknown
EGFR V843L unknown
EGFR E709Q unknown
EGFR E746_T751delinsV gain of function - predicted
EGFR I941R loss of function
EGFR E884K unknown
EGFR T790M MET amp
EGFR T790M ERBB2 over exp
EGFR T790M gain of function EGFR Inhibitor 3rd gen PF-06747775
EGFR L747_T751delinsP EGFR T790M
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 S768N no effect
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 E866K loss of function
EGFR I740_K745dup gain of function - predicted
EGFR D770_N771insSVE gain of function - predicted
EGFR L844V no effect - predicted
EGFR H988P unknown
EGFR exon 19 ins gain of function
EGFR S720Y unknown
EGFR V689M gain of function EGFR Inhibitor (Pan) EGFR Inhibitor 1st gen EGFR Inhibitor 2nd gen EGFR Inhibitor 3rd gen HER inhibitor (Pan)
EGFR S380Pfs*16 loss of function - predicted
EGFR M766_A767insAI gain of function - predicted
EGFR A743T unknown
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
EGFR D770_N771insNPY non-small cell lung 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 S768I Advanced Solid Tumor decreased response Erlotinib Clinical Study Actionable In a retrospective clinical study, non-small lung cancer patients harboring EGFR S768I demonstrated a median progression-free survival of 2.7 months following treatment with EGFR tyrosine kinase inhibitors such as Tarceva (erlotinib), Iressa (gefitinib), or Icotinib, compared to 10.8 months in patients with EGFR L858R and EGFR exon 19 deletions (PMID: 27468240). 27468240
EGFR S768I Advanced Solid Tumor decreased response Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR S768I had decreased sensitivity to Tarceva (erlotinib) in cell culture (PMID: 19147750). 19147750
EGFR S768I Advanced Solid Tumor resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR S768I were resistant to treatment with Erbitux (cetuximab) in culture (PMID: 29141884). 29141884
EGFR S768I non-small cell lung carcinoma decreased response Icotinib Clinical Study Actionable In a retrospective analysis, non-small cell lung cancer patients harboring EGFR S768I demonstrated a response rate of 25% and disease control rate of 80%, and a median progression-free survival of 3.2 months following treatment with icotinib (J Clin Oncol 35, 2017 (suppl; abstr e14050)). detail...
EGFR S768I non-small cell lung carcinoma decreased response Icotinib Clinical Study Actionable In a retrospective clinical study, non-small cell lung cancer patients harboring EGFR S768I demonstrated a median progression-free survival of 2.7 months following treatment with EGFR tyrosine kinase inhibitors such as Tarceva (erlotinib), Iressa (gefitinib), or icotinib, compared to 10.8 months in patients with EGFR L858R and EGFR exon 19 deletions (PMID: 27468240). 27468240
EGFR S768I Advanced Solid Tumor resistant Gefitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR S768I were resistant to treatment with Iressa (gefitinib) in culture (PMID: 29141884). 29141884
EGFR S768I non-small cell lung carcinoma decreased response Gefitinib Clinical Study Actionable In a retrospective clinical study, non-small lung cancer patients harboring EGFR S768I demonstrated a median progression-free survival of 2.7 months following treatment with EGFR tyrosine kinase inhibitors such as Tarceva (erlotinib), Iressa (gefitinib), or Icotinib, compared to 10.8 months in patients with EGFR L858R and EGFR exon 19 deletions (PMID: 27468240). 27468240
EGFR S768I Advanced Solid Tumor resistant CO1686 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR S768I were resistant to treatment with Rociletinib (CO-1686) in culture (PMID: 29141884). 29141884
EGFR S768I non-small cell lung carcinoma predicted - sensitive Poziotinib Phase II Actionable In a Phase II trial, treatment with Poziotinib (HM781-36B) resulted in objective partial responses in 64% (7/11) of patients with non-small cell lung cancer harboring EGFR exon 20 mutations, including a patient with EGFR S768I (PMID: 29686424; NCT03066206). 29686424
EGFR S768I non-small cell lung carcinoma sensitive Afatinib FDA approved Actionable In a post-hoc analysis of Phase II and Phase III trials that supported FDA approval (LUX-Lung 2, LUX-Lung 3, LUX-Lung 6), Gilotrif (afatinib) treatment resulted in partial response in 100% (8/8) of non-small cell lung cancer patients harboring EGFR S768I (alone or in combination with EGFR L719X or L858R), with a mean progression-free survival of 14.7 months (PMID: 26051236; NCT00525148, NCT00949650, and NCT01121393). 26051236
EGFR S768I non-small cell lung carcinoma sensitive Afatinib Clinical Study Actionable In a prospective clinical study, Gilotrif (afatinib) treatment resulted in stable disease in a non-small cell lung carcinoma patient harboring EGFR S768I (PMID: 26354527). 26354527
EGFR I491M colorectal cancer sensitive MM-151 Preclinical Actionable In a preclinical study, MM-151 inhibited survival of colorectal cancer cell lines over expressing EGFR I491M in culture (PMID: 26843189). 26843189
EGFR I491M colorectal cancer resistant Cetuximab Preclinical Actionable In a preclinical study, colorectal cancer cell lines over expressing EGFR I491M were resistant to Erbitux (cetuximab)-induced growth inhibition in culture (PMID: 26843189). 26843189
EGFR I491M colorectal cancer resistant Panitumumab Preclinical Actionable In a preclinical study, colorectal cancer cell lines over expressing EGFR I491M were resistant to Vectibix (panitumumab)-induced growth inhibition in culture (PMID: 26843189). 26843189
EGFR K745_E746insVPVAIK Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR K745_E746insVPVAIK were sensitive to treatment with Tagrisso (osimertinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR K745_E746insVPVAIK Advanced Solid Tumor resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR K745_E746insVPVAIK were resistant to treatment with Erbitux (cetuximab) in culture (PMID: 29141884). 29141884
EGFR K745_E746insVPVAIK Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR K745_E746insVPVAIK were sensitive to treatment with Gilotrif (afatinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR R252C Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR R252C were sensitive to treatment with Gilotrif (afatinib) in culture (PMID: 29141884). 29141884
EGFR E746_A750delinsIP Advanced Solid Tumor sensitive Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR E746_A750delinsIP were sensitive to treatment with Tarceva (erlotinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR E746_A750delinsIP Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR E746_A750delinsIP were sensitive to treatment with Tagrisso (osimertinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR E746_A750delinsIP Advanced Solid Tumor resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR E746_A750delinsIP were resistant to treatment with Erbitux (cetuximab) in culture (PMID: 29141884). 29141884
EGFR E746_A750delinsIP Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR E746_A750delinsIP were sensitive to treatment with Gilotrif (afatinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR E746_A750delinsIP Advanced Solid Tumor sensitive Gefitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR E746_A750delinsIP were sensitive to treatment with Iressa (gefitinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR E746_A750delinsIP Advanced Solid Tumor sensitive CO1686 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR E746_A750delinsIP were sensitive to treatment with Rociletinib (CO-1686) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR P596L Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR P596L were sensitive to treatment with Tagrisso (osimertinib) in culture (PMID: 29141884). 29141884
EGFR P596L Advanced Solid Tumor sensitive Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR P596L were sensitive to treatment with Erbitux (cetuximab) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR P596L Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR P596L were sensitive to treatment with Gilotrif (afatinib) in culture (PMID: 29141884). 29141884
EGFR S720F Advanced Solid Tumor sensitive Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR S720F were sensitive to treatment with Tarceva (erlotinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR S720F Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR S720F were sensitive to treatment with Tagrisso (osimertinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR S720F Advanced Solid Tumor sensitive Gefitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR S720F were sensitive to treatment with Iressa (gefitinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR S720F Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR S720F were sensitive to treatment with Gilotrif (afatinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR S720F Advanced Solid Tumor resistant CO1686 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR S720F were resistant to treatment with Rociletinib (CO-1686) in culture (PMID: 29141884). 29141884
EGFR S720F Advanced Solid Tumor sensitive Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR S720F were sensitive to treatment with Erbitux (cetuximab) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR D770_N771insGF non-small cell lung 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 A767_V769dup Advanced Solid Tumor resistant Dacomitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A767_V769dup (also referred to as V769_D770insASV) demonstrated resistance to Vizimpro (dacomitinib) in culture (PMID: 28363995). 28363995
EGFR A767_V769dup Advanced Solid Tumor resistant CO1686 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A767_V769dup (reported as V769_D770insASV) were resistant to treatment with Rociletinib (CO-1686) in culture (PMID: 29141884). 29141884
EGFR A767_V769dup Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A767_V769dup (reported as V769_D770insASV) were sensitive to treatment with Tagrisso (osimertinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR A767_V769dup Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, Tagrisso (osimertinib) inhibited EGFR signaling and proliferation of transformed cells expressing EGFR A767_V769dup in culture (PMID: 29467275). 29467275
EGFR A767_V769dup Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, Tagrisso (osimertinib) inhibited Egfr phosphorylation in transformed cells expressing EGFR A767_V769dup (reported as V769_D770insASV) in culture (PMID: 29483211). 29483211
EGFR A767_V769dup Advanced Solid Tumor resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A767_V769dup were resistant to Tarceva (erlotinib) in culture (PMID: 29467275). 29467275
EGFR A767_V769dup Advanced Solid Tumor resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A767_V769dup (reported as V769_D770insASV) were resistant to treatment with Tarceva (erlotinib) in culture (PMID: 29141884). 29141884
EGFR A767_V769dup Advanced Solid Tumor resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A767_V769dup (reported as V769_D770insASV) were insensitive to Tarceva (erlotinib)-mediated inhibition of Egfr phosphorylation in culture (PMID: 29483211). 29483211
EGFR A767_V769dup Advanced Solid Tumor resistant Gefitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A767_V769dup (reported as V769_D770insASV) were resistant to treatment with Iressa (gefitinib) in culture (PMID: 29141884). 29141884
EGFR A767_V769dup Advanced Solid Tumor predicted - sensitive TAS6417 Preclinical - Cell culture Actionable In a preclinical study, TAS6417 inhibited EGFR phosphorylation and proliferation of cells expressing EGFR exon 20 insertion mutations, including EGFR A767_V769dup (reported as V769_D770insASV), in culture (PMID: 29748209). 29748209
EGFR A767_V769dup non-small cell lung carcinoma predicted - sensitive Poziotinib Phase II Actionable In a Phase II trial, treatment with Poziotinib (HM781-36B) resulted in objective partial responses in 64% (7/11) of patients with non-small cell lung cancer harboring EGFR exon 20 mutations, including a patient with EGFR A767_V769dup (PMID: 29686424; NCT03066206). 29686424
EGFR A767_V769dup Advanced Solid Tumor conflicting Afatinib Preclinical - Cell culture Actionable In a preclinical study, Gilotrif (afatinib) inhibited EGFR signaling and proliferation of transformed cells expressing EGFR A767_V769dup in culture (PMID: 29467275). 29467275
EGFR A767_V769dup Advanced Solid Tumor conflicting Afatinib Clinical Study Actionable In a preclinical study, transformed cells expressing EGFR exon 20 insertions, including EGFR A767_V769dup (reported as V769_D770insASV), demonstrated resistance to Gilotrif (afatinib) in cell culture (PMID: 24353160, PMID: 29141884). 29141884 24353160
EGFR A767_V769dup Advanced Solid Tumor sensitive Poziotinib Preclinical - Cell culture Actionable In a preclinical study, Poziotinib (HM781-36B) inhibited growth of transformed cell lines expressing EGFR A767_V769dup (reported as V769insASV) in culture (PMID: 29686424). 29686424
EGFR A767_V769dup non-small cell lung carcinoma resistant Erlotinib Phase I Actionable In a retrospective analysis, non-small cell lung cancer patients harboring EGFR exon 20 insertions, such as EGFR A767_V769dup (reported as V769_D770insASV), displayed progressive disease following treatment with Tarceva (erlotinib), and resistance to Tarceva (erlotinib) was replicated in cell culture studies (PMID: 24353160). 24353160
EGFR A767_V769dup lung cancer sensitive TAS6417 Preclinical - Pdx & cell culture Actionable In a preclinical study, TAS6417 inhibited growth and induced apoptotic markers in a lung cancer patient-derived xenograft (PDX) model-derived cell line harboring EGFR A767_V769dup (reported as V769_D770insASV) in culture, and inhibited tumor growth and induced tumor regression in PDX models (PMID: 29748209). 29748209
EGFR A767_V769dup non-small cell lung carcinoma resistant Afatinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells expressing EGFR A767_V769dup (reported as V769_D770insASV) were resistant to Gilotrif (afatinib)-mediated growth inhibition in culture and in cell line xenograft models (PMID: 29483211). 29483211
EGFR A767_V769dup non-small cell lung carcinoma resistant Afatinib Preclinical - Pdx Actionable In a preclinicl study, patient-derived xenograft (PDX) models of non-small cell lung cancer harboring EGFR A767_V769dup (reported as M766_A767insASV) were resistant to Gilotrif (afatinib) (PMID: 29483211). 29483211
EGFR A767_V769dup non-small cell lung 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 of 3 patient harboring EGFR A767_V769dup achieved stable disease (PMID: 30351341; NCT01854034). 30351341
EGFR A767_V769dup non-small cell lung carcinoma resistant Gefitinib Clinical Study Actionable In a retrospective analysis, non-small cell lung cancer patients harboring EGFR exon 20 insertions, such as EGFR A767_V769dup (reported as V769_D770insASV), displayed progressive disease following treatment with Iressa (gefitinib), and resistance to Iressa (gefitinib) was replicated in cell culture studies (PMID: 24353160). 24353160
EGFR A767_V769dup Advanced Solid Tumor sensitive Naquotinib Preclinical - Cell culture Actionable In a preclinical study, Naquotinib (ASP8273) inhibited EGFR signaling and proliferation of transformed cells expressing EGFR A767_V769dup in culture (PMID: 29467275). 29467275
EGFR A767_V769dup lung adenocarcinoma sensitive Poziotinib Preclinical - Patient cell culture Actionable In a preclinical study, Poziotinib (HM781-36B) inhibited EGFR phosphorylation and growth of a lung adenocarcinoma patient cell line harboring EGFR A767_V769dup in culture (PMID: 29686424). 29686424
EGFR A767_V769dup Advanced Solid Tumor sensitive Nazartinib Preclinical - Cell culture Actionable In a preclinical study, EGF816 inhibited growth of transformed cells expressing EGFR A767_V769dup (reported as V769_D770insASV) in culture (PMID: 26825170). 26825170
EGFR A767_V769dup non-small cell lung carcinoma sensitive Osimertinib Preclinical - Pdx Actionable In a preclinical study, Tagrisso (osimertinib) inhibited tumor growth in patient-derived xenograft (PDX) models of non-small cell lung cancer harboring EGFR A767_V769dup (reported as M766_A767insASV) (PMID: 29483211). 29483211
EGFR A767_V769dup non-small cell lung carcinoma sensitive Osimertinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Tagrisso (osimertinib) inhibited Egfr phosphorylation, resulted in growth inhibition of non-small cell lung carcinoma cells expressing EGFR A767_V769dup (reported as V769_D770insASV) in culture, and tumor regression in cell line and patient-derived xenograft (PDX) models (PMID: 29483211). 29483211
EGFR A767_V769dup lung cancer 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 A767_V769dup 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 A767_V769dup lung cancer predicted - resistant Afatinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Gilotrif (afatinib) decreased Egfr signaling and proliferation of patient-derived lung cancer cells harboring EGFR A767_V769dup in culture, bud did not affect tumor growth in patient-derived xenograft (PDX) models (Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A157). detail...
EGFR L747_S752del EGFR T790M lung adenocarcinoma resistant Gefitinib Clinical Study Actionable In a retrospective analysis, a patient with lung adenocarcinoma harboring EGFR L747_S752del that developed Iressa (gefitinib) resistance was demonstrated to have acquired an EGFR T790M mutation (PMID: 18981003). 18981003
EGFR L747_S752del EGFR T790M lung adenocarcinoma resistant Erlotinib Clinical Study Actionable In a retrospective analysis, a patient with lung adenocarcinoma harboring EGFR L747_S752del and EGFR T790M was found to rapidly progress on Tarceva (erlotinib) therapy (PMID: 18981003). 18981003
EGFR L747_S752del lung adenocarcinoma sensitive Gefitinib Clinical Study Actionable In a retrospective analysis, a patient with lung adenocarcinoma harboring EGFR L747_S752del had a partial response to Iressa (gefitinib) therapy (PMID: 18981003). 18981003
EGFR L747_T751del EGFR S752I non-small cell lung carcinoma sensitive WZ4002 + Trametinib 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 G598V Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR G598V were sensitive to treatment with Gilotrif (afatinib) in culture (PMID: 29141884). 29141884
EGFR G598V Advanced Solid Tumor sensitive Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR G598V were sensitive to treatment with Erbitux (cetuximab) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR G598V Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR G598V were sensitive to treatment with Tagrisso (osimertinib) in culture (PMID: 29141884). 29141884
EGFR G598V Advanced Solid Tumor resistant CO1686 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR G598V were resistant to treatment with Rociletinib (CO-1686) in culture (PMID: 29141884). 29141884
EGFR G696_P1033dup Advanced Solid Tumor sensitive Osimertinib Preclinical Actionable In a preclinical study, Tagrisso (osimertinib) inhibited EGFR phosphorylation and cell proliferation in transformed cells expressing kinase domain duplication mutant EGFR G696_P1033dup in culture (PMID: 26286086). 26286086
EGFR G696_P1033dup Advanced Solid Tumor sensitive Erlotinib Preclinical Actionable In a preclinical study, Tarceva (erlotinib) inhibited EGFR phosphorylation and cell proliferation in transformed cells expressing the kinase domain duplication mutant EGFR G696_P1033dup in culture (PMID: 26286086). 26286086
EGFR G696_P1033dup lung adenocarcinoma sensitive Afatinib Clinical Study Actionable In a clinical study, a patient with EGFR G696_P1033dup expressing lung adenocarcinoma had a partial response after two cycles of Gilotrif (afatinib) after failing first line chemotherapy (PMID: 26286086). 26286086
EGFR G696_P1033dup Advanced Solid Tumor sensitive Afatinib Preclinical Actionable In a preclinical study, Gilotrif (afatinib) inhibited EGFR phosphorylation and cell proliferation in transformed cells expressing kinase domain duplication mutant EGFR G696_P1033dup in culture (PMID: 26286086). 26286086
EGFR amp EGFR G696_P1033dup lung adenocarcinoma resistant Afatinib Clinical Study Actionable In a clinical case study, a patient with EGFR G696_P1033dup expressing lung adenocarcinoma 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 E746_S752del EGFR T790M EGFR P794L non-small cell lung carcinoma predicted - resistant Osimertinib Clinical Study 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 E746_S752del EGFR T790M EGFR P794L non-small cell lung carcinoma predicted - sensitive Afatinib Clinical Study 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 V292L Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR V292L were sensitive to treatment with Gilotrif (afatinib) in culture (PMID: 29141884). 29141884
EGFR V292L Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR V292L were sensitive to treatment with Tagrisso (osimertinib) in culture (PMID: 29141884). 29141884
EGFR V292L Advanced Solid Tumor sensitive Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR V292L were sensitive to treatment with Erbitux (cetuximab) in culture (PMID: 29141884). 29141884
EGFR G719C non-small cell lung carcinoma sensitive Dacomitinib Phase III Actionable In Phase III clinical trials, patients with NSCLC tumors harboring an EGFR G719X (X=A, C, or S) mutation responded to EGFR tyrosine kinase inhibitors including Vizimpro (dacomitinib) (PMID: 24857124). 24857124
EGFR G719C non-small cell lung carcinoma predicted - sensitive Erlotinib Clinical Study Actionable In an analysis of published clinical data, 14/18 (78%) non-small cell lung cancer patients harboring an EGFR G719X (X=A, C, D, or S) mutation were found to achieve disease control following treatment with EGFR tyrosine kinase inhibitors, such as Tarceva (erlotinib) (PMID: 23344264). 23344264
EGFR G719C non-small cell lung carcinoma predicted - sensitive Gefitinib Clinical Study Actionable In an analysis of published clinical data, 14/18 (78%) non-small cell lung cancer patients harboring an EGFR G719X (X=A, C, D, or S) mutation were found to achieve disease control following treatment with EGFR tyrosine kinase inhibitors, such as Iressa (gefitinib) (PMID: 23344264). 23344264
EGFR G719C non-small cell lung carcinoma sensitive Afatinib Phase III Actionable In Phase III trials, non-small cell lung carcinoma patients harboring EGFR G719X mutations (G719A, C, or S) demonstrated a response rate of 78% (14/18) following treatment with Gilotrif (afatinib) (PMID: 24790411). 24790411
EGFR G719C Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR E719C were sensitive to treatment with Tagrisso (osimertinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR G719C Advanced Solid Tumor resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR G719C were resistant to treatment with Erbitux (cetuximab) in culture (PMID: 29141884). 29141884
EGFR G719A EGFR L861Q EGFR T790M lung adenocarcinoma predicted - resistant Erlotinib Clinical Study Actionable In a clinical case study, EGFR T790M was detected at the time of progression in a patient with lung adenocarcinoma harboring EGFR G719A and L861Q that was treated with Tarceva (erlotinib) (PMID: 28343545). 28343545
EGFR G719A EGFR L861Q EGFR T790M lung adenocarcinoma predicted - sensitive Osimertinib Clinical Study Actionable In a clinical case study, Tagrisso (osimertinib) treatment resulted in partial response for over 8 months in a patient with lung adenocarcinoma harboring EGFR G719A, L861Q, and T790M that has progressed while on Tarceva (erlotinib) treatment (PMID: 28343545). 28343545
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
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 G719A EGFR T790M Advanced Solid Tumor resistant Afatinib Preclinical - Cell culture Actionable In a preclinical study, acquisition of EGFR T790M was associated with resistance to Gilotrif (afatinib) in transformed cells expressing EGFR G719A in culture (PMID: 27913578). 27913578
EGFR G719A EGFR L861Q lung adenocarcinoma predicted - sensitive Erlotinib Clinical Study Actionable In a clinical case study, Tarceva (erlotinib) treatment resulted in partial response lasting for 18 months in a patient with lung adenocarcinoma harboring EGFR G719A and L861Q (PMID: 28343545). 28343545
EGFR G719A Advanced Solid Tumor decreased response Erlotinib Preclinical Actionable In a preclinical study, transformed cells expressing EGFR G719A demonstrated decreased sensitivity to first-generation EGFR inhibitors including Tarceva (erlotinib) in culture, when compared to second-generation inhibitors (PMID: 26206867). 26206867
EGFR G719A Advanced Solid Tumor sensitive Dacomitinib Preclinical Actionable In a preclinical study, transformed cells expressing EGFR G719A 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 G719A non-small cell lung carcinoma predicted - sensitive Gefitinib Clinical Study Actionable In an analysis of published clinical data, 7/11 non-small cell lung cancer patients harboring EGFR G719A were found to achieve disease control following treatment with EGFR tyrosine kinase inhibitors, such as Iressa (gefitinib) (PMID: 23344264). 23344264
EGFR G719A non-small cell lung carcinoma sensitive Dacomitinib Phase III Actionable In Phase III clinical trials, patients with NSCLC tumors harboring an EGFR G719X (X=A, C, or S) mutation responded to EGFR tyrosine kinase inhibitors including Vizimpro (dacomitinib) (PMID: 24857124). 24857124
EGFR G719A Advanced Solid Tumor sensitive Neratinib Preclinical Actionable In a preclinical study, transformed cells expressing EGFR G719A 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 G719A Advanced Solid Tumor decreased response CO1686 Preclinical Actionable In a preclinical study, transformed cells expressing EGFR G719A demonstrated decreased sensitivity to third-generation EGFR inhibitors including Rociletinib (CO-1686) in culture, when compared to second-generation inhibitors (PMID: 26206867). 26206867
EGFR G719A Advanced Solid Tumor sensitive Afatinib Preclinical Actionable In a preclinical study, transformed cells expressing EGFR G719A 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 G719A Advanced Solid Tumor decreased response Osimertinib Preclinical Actionable In a preclinical study, transformed cells expressing EGFR G719A demonstrated decreased sensitivity to third-generation EGFR inhibitors including Tagrisso (AZD9291) in culture, when compared to second-generation inhibitors (PMID: 26206867). 26206867
EGFR G719A non-small cell lung carcinoma sensitive Afatinib Phase III Actionable In Phase III trials, non-small cell lung carcinoma patients harboring EGFR G719X mutations (G719A, C, or S) demonstrated a response rate of 78% (14/18) following treatment with Gilotrif (afatinib) (PMID: 24790411). 24790411
EGFR G719A Advanced Solid Tumor sensitive AP32788 Preclinical - Cell culture Actionable In a preclinical study, AP32788 inhibited growth of transformed cell lines over expressing EGFR G719A in culture (AACR, Cancer Res: April 2016; Volume 57, Abstract #2644). detail...
EGFR G719A non-small cell lung carcinoma predicted - sensitive Erlotinib Clinical Study Actionable In an analysis of published clinical data, 7/11 non-small cell lung cancer patients harboring EGFR G719A were found to achieve disease control following treatment with EGFR tyrosine kinase inhibitors, such as Tarceva (erlotinib) (PMID: 23344264). 23344264
EGFR G719A Advanced Solid Tumor decreased response Gefitinib Preclinical Actionable In a preclinical study, transformed cells expressing EGFR G719A demonstrated decreased sensitivity to first-generation EGFR inhibitors including Iressa (gefitinib) in culture, when compared to second-generation inhibitors (PMID: 26206867). 26206867
EGFR G719A Advanced Solid Tumor resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR G719A were resistant to treatment with Erbitux (cetuximab) in culture (PMID: 29141884). 29141884
EGFR A289V Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A289V were sensitive to treatment with Gilotrif (afatinib) in culture (PMID: 29141884). 29141884
EGFR A289V Advanced Solid Tumor sensitive Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A289V were sensitive to treatment with Erbitux (cetuximab) in culture, demonstrating decreased cell viability (PMID: 29141884). 29141884
EGFR A289V Advanced Solid Tumor sensitive Erlotinib Preclinical Actionable In a preclinical study, Tarceva (erlotinib) decreased viability of transformed cells expressing EGFR A289V in culture (PMID: 17177598). 17177598
EGFR A289V Advanced Solid Tumor resistant CO1686 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A289V were resistant to treatment with Rociletinib (CO-1686) in culture (PMID: 29141884). 29141884
EGFR A289V Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A289V were sensitive to treatment with Tagrisso (osimertinib) in culture (PMID: 29141884). 29141884
EGFR N771_H773dup Advanced Solid Tumor sensitive Poziotinib Preclinical - Cell culture Actionable In a preclinical study, Poziotinib (HM781-36B) inhibited EGFR phosphorylation and growth of a transformed cell line expressing EGFR N771_H773dup (reported as H773insNPH) in culture (PMID: 29686424). 29686424
EGFR N771_H773dup lung adenocarcinoma sensitive Dacomitinib Preclinical - Patient cell culture Actionable In a preclinical study, Vizimpro (dacomitinib) inhibited EGFR phosphorylation and growth of a patient-derived lung adenocarcinoma cell line harboring EGFR N771_H773dup (also referred to as H773_V774insNPH) in culture (PMID: 28363995). 28363995
EGFR N771_H773dup non-small cell lung carcinoma sensitive Poziotinib Preclinical - Pdx Actionable In a preclinical study, treatment with Poziotinib (HM781-36B) decreased tumor burden by greater than 85% in 8/9 mice in a patient-derived xenograft (PDX) model of non-small cell lung cancer harboring EGFR N771_H773dup (reported as EGFR H773insNPH) (PMID: 29686424). 29686424
EGFR N771_H773dup Advanced Solid Tumor sensitive Nazartinib Preclinical - Cell culture Actionable In a preclinical study, EGF816 inhibited growth of transformed cells expressing EGFR N771_H773dup (reported as H773_V774insNPH) in culture (PMID: 26825170). 26825170
EGFR N771_H773dup head and neck squamous cell carcinoma resistant Gefitinib Preclinical Actionable In a preclinical study, sinonasal squamous cell carcinoma cells harboring EGFR N771_H773dup demonstrated resistance to Iressa (gefinitib) in culture (PMID: 25931286). 25931286
EGFR N771_H773dup lung cancer predicted - resistant Afatinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Gilotrif (afatinib) decreased Egfr signaling and proliferation of patient-derived lung cancer cells harboring EGFR N771_H773dup in culture, bud did not affect tumor growth in patient-derived xenograft (PDX) models (Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A157). detail...
EGFR N771_H773dup non-small cell lung carcinoma sensitive Nazartinib Preclinical - Pdx Actionable In a preclinical study, EGF816 inhibited tumor growth in patient-derived xenograft models of non-small cell lung cancer harboring EGFR N771_H773dup (reported as H773_V774insNPH) (PMID: 26825170). 26825170
EGFR N771_H773dup lung cancer 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 N771_H773dup 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 N771_H773dup head and neck squamous cell carcinoma resistant Erlotinib Preclinical Actionable In a preclinical study, sinonasal squamous cell carcinoma cells harboring EGFR N771_H773dup demonstrated resistance to Tarceva (erlotinib) in culture (PMID: 25931286). 25931286
EGFR N771_H773dup lung adenocarcinoma sensitive Afatinib Preclinical - Patient cell culture Actionable In a preclinical study, Gilotrif (afatinib) inhibited EGFR phosphorylation and growth of a patient-derived lung adenocarcinoma cell line harboring EGFR N771_H773dup (also referred to as H773_V774insNPH) in culture (PMID: 28363995). 28363995
EGFR N771_H773dup non-small cell lung carcinoma sensitive Osimertinib Preclinical - Pdx Actionable In a preclinical study, Tagrisso (osimertinib) treatment resulted in tumor regression in patient-derived xenograft (PDX) models of non-small cell lung cancer harboring EGFR N771_H773dup (reported as H773_V774insNPH) (PMID: 29483211). 29483211
EGFR N771_H773dup head and neck squamous cell carcinoma sensitive Neratinib Preclinical Actionable In a preclinical study, Nerlynx (neratinib) inhibited growth of sinonasal squamous cell carcinoma cells harboring EGFR N771_H773dup in culture (PMID: 25931286). 25931286
EGFR N771_H773dup Advanced Solid Tumor sensitive TAS6417 Preclinical - Cell line xenograft Actionable In a preclinical study, TAS6417 inhibited EGFR phosphorylation and proliferation of cells expressing EGFR exon 20 insertion mutations, including EGFR N771_H773dup (reported as H773_V774insNPH), in culture, and inhibited tumor growth in cell line xenograft models (PMID: 29748209). 29748209
EGFR N771_H773dup lung cancer predicted - sensitive TAS6417 Preclinical - Pdx Actionable In a preclinical study, TAS6417 inhibited tumor growth in lung cancer patient-derived xenograft (PDX) models harboring EGFR N771_H773dup (reported as H773_V774insNPH) (PMID: 29748209). 29748209
EGFR G465E EGFR G465R colorectal cancer sensitive MM-151 Phase I Actionable In a Phase I trial, MM-151 treatment resulted in marked reduction of EGFR G465E in circulating cell-free tumor DNA and reduced tumor size in a colorectal cancer patient harboring both EGFR G465E and EGFR G465R (PMID: 26843189). 26843189
EGFR G465E colorectal cancer resistant Cetuximab Preclinical Actionable In a preclinical study, colorectal cancer cell lines over expressing EGFR G465E were resistant to Erbitux (cetuximab)-induced growth inhibition in culture (PMID: 26843189). 26843189
EGFR G465E colorectal cancer resistant Panitumumab Preclinical Actionable In a preclinical study, colorectal cancer cell lines over expressing EGFR G465E were resistant to Vectibix (panitumumab)-induced growth inhibition in culture (PMID: 26843189). 26843189
EGFR G465E colorectal cancer sensitive MM-151 Preclinical Actionable In a preclinical study, MM-151 inhibited survival of colorectal cancer cell lines over expressing EGFR G465E in culture (PMID: 26843189). 26843189
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 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 Erdafitinib (JNJ-42756493) in culture (PMID: 28341788). 28341788
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
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 gastric adenocarcinoma predicted - sensitive Cetuximab Clinical Study Actionable In a clinical analysis, anti-Egfr antibody therapies including Erbitux (cetuximab) and ABT-806, alone or in combination with chemotherapy, resulted in 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 (PMID: 29449271). 29449271
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 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 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 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 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 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 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 esophagus adenocarcinoma resistant AMG 337 Clinical Study 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 ABT-806 Clinical Study Actionable In a clinical analysis, anti-Egfr antibody therapies including Erbitux (cetuximab) and ABT-806, alone or in combination with chemotherapy, resulted in 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 (PMID: 29449271). 29449271
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 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 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 gastroesophageal junction adenocarcinoma predicted - sensitive Cetuximab Clinical Study Actionable In a clinical analysis, anti-Egfr antibody therapies including Erbitux (cetuximab) and ABT-806, alone or in combination with chemotherapy, resulted in 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 (PMID: 29449271). 29449271
EGFR amp head and neck cancer sensitive EGFR antibody + ERBB3 antibody + 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 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 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 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 glioblastoma multiforme no benefit Vandetanib + Temozolomide 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 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 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 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 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 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 gastric adenocarcinoma predicted - sensitive ABT-806 Clinical Study Actionable In a clinical analysis, anti-Egfr antibody therapies including Erbitux (cetuximab) and ABT-806, alone or in combination with chemotherapy, resulted in 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 (PMID: 29449271). 29449271
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 non-small cell lung 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 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 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 non-small cell lung 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 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 Temsirolimus + Erlotinib 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 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 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 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 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 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 S492R BRAF V600E colorectal cancer resistant Cetuximab Clinical Study Actionable In a clinical study, a colorectal cancer patient harboring EGFR amplification, BRAF V600E, and EGFR S492R demonstrated resistance to Erbitux (cetuximab) (PMID: 22270724). 22270724
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 EGFR amp glioblastoma multiforme predicted - sensitive Depatuxizumab mafodotin + Temozolomide + Radiotherapy 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 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 MET amp non-small cell lung carcinoma predicted - resistant Erlotinib Clinical Study 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 MET amplification (PMID: 30268451). 30268451
EGFR amp MET amp non-small cell lung carcinoma predicted - resistant Osimertinib Clinical Study 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 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 non-small cell lung carcinoma predicted - resistant Gefitinib Clinical Study 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 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
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 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 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 Vemurafenib + 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) 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 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 + 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 + 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 Trametinib + Dabrafenib 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 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
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
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 amp ERBB2 over exp stomach cancer predicted - resistant Trastuzumab Clinical Study 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
EML4-ALK EGFR amp non-small cell lung carcinoma predicted - resistant Crizotinib Clinical Study 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 colorectal cancer sensitive Panitumumab Clinical Study Actionable In a clinical study, a colorectal cancer patient harboring both EGFR amplification and EGFR S492R demonstrated a 50% tumor reduction when treated with Vectibix (panitumumab) (PMID: 22270724). 22270724
EGFR amp EGFR S492R colorectal cancer resistant Cetuximab Clinical Study Actionable In a clinical study, a colorectal cancer patient harboring EGFR amplification and EGFR S492R demonstrated resistance to Erbitux (cetuximab) (PMID: 22270724). 22270724
EGFR amp FGFR1 amp KRAS G13C lung cancer resistant Erdafitinib Preclinical - Cell culture Actionable In a preclinical study, a lung cancer cell line with co-amplification of FGFR1 and EGFR and harboring KRAS G13C demonstrated insensitivity to Erdafitinib (JNJ-42756493) in culture (PMID: 28341788). 28341788
EGFR act mut EGFR C797S EGFR T790M non-small cell lung 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 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 non-small cell lung 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 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 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 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 act mut EGFR T790M non-small cell lung 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 act mut EGFR T790M non-small cell lung 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 non-small cell lung 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 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 non-small cell lung 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 non-small cell lung 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 non-small cell lung 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 non-small cell lung carcinoma sensitive CO1686 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 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 non-small cell lung 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 act mut non-small cell lung 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 act mut non-small cell lung 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) (PMID: 28169392). 28169392
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 non-small cell lung 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 non-small cell lung 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 non-small cell lung 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 non-small cell lung 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 non-small cell lung 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 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 non-small cell lung 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 non-small cell lung 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 non-small cell lung 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 non-small cell lung 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 act mut non-small cell lung 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 non-small cell lung 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 non-small cell lung carcinoma predicted - sensitive Glesatinib + Erlotinib 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 non-small cell lung carcinoma sensitive Osimertinib Guideline Actionable Tagrisso (osimertinib) is included in guidelines as first-line therapy for locally advanced or metastatic non-small cell lung carcinoma patients harboring sensitizing EGFR mutations, including exon 19 deletion and L858R (NCCN.org). detail...
EGFR act mut non-small cell lung 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 non-small cell lung carcinoma predicted - 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 non-small cell lung carcinoma predicted - 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 non-small cell lung carcinoma predicted - sensitive Erlotinib Guideline Actionable Tarceva (erlotinib) 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 D770_N771insSVD non-small cell lung 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, resulted in 1 partial response and 1 stable disease in 3 patients harboring EGFR D770_N771insSVD (PMID: 30351341; NCT01854034). 30351341
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 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 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 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 R521K FGFR2 M186T KDR Q472H KDR V297I RET M1009T olfactory neuroblastoma sensitive Cetuximab + Sunitinib Clinical Study Actionable In clinical case study, a patient with olfactory neuroblastoma harboring EGFR R521K, FGFR2 M186T, KDR Q472H, KDR V297I, and RET M1009T demonstrated sensitivity to the combination of Sutent (sunitinib) and Erbitux (cetuximab), resulting in a complete response (PMID: 27149458). 27149458
EGFR A289D Advanced Solid Tumor sensitive Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A289D were sensitive to treatment with Erbitux (cetuximab) in culture, demonstrating decreased cell viability (PMID: 29141884). 29141884
EGFR A289D Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A289D were sensitive to treatment with Tagrisso (osimertinib) in culture (PMID: 29141884). 29141884
EGFR L747S Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR L747S were sensitive to treatment with Tagrisso (osimertinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR L747S Advanced Solid Tumor resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR L747S were resistant to treatment with Erbitux (cetuximab) in culture (PMID: 29141884). 29141884
EGFR L747S Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR L747S were sensitive to treatment with Gilotrif (afatinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR L858R EGFR L747S lung adenocarcinoma resistant Gefitinib Clinical Study Actionable In a retrospective analysis, a patient with lung adenocarcinoma harboring EGFR L858R that had developed Iressa (gefitinib) resistance was demonstrated to have acquired an EGFR L747S mutation (PMID: 18981003). 18981003
EGFR L858R EGFR L747S lung adenocarcinoma decreased response Erlotinib Clinical Study Actionable In a retrospective analysis, a patient with lung adenocarcinoma harboring EGFR L858R and EGFR L747S had an initial partial response to Tarceva (erlotinib), but was found to progress after 6 months (PMID: 18981003). 18981003
EGFR L747_T751delinsS Advanced Solid Tumor resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR L747_T751delinsS were resistant to treatment with Erbitux (cetuximab) in culture (PMID: 29141884). 29141884
EGFR L747_T751delinsS Advanced Solid Tumor sensitive CO1686 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR L747_T751delinsS were sensitive to treatment with Rociletinib (CO-1686) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR L747_T751delinsS Advanced Solid Tumor sensitive Gefitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR L747_T751delinsS were sensitive to treatment with Iressa (gefitinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR L747_T751delinsS Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR L747_T751delinsS were sensitive to treatment with Gilotrif (afatinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR L747_T751delinsS Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR L747_T751delinsS were sensitive to treatment with Tagrisso (osimertinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR L747_T751delinsS Advanced Solid Tumor sensitive Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR L747_T751delinsS were sensitive to treatment with Tarceva (erlotinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR D770_N771insGV non-small cell lung 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-RAD51 lung adenocarcinoma sensitive Erlotinib Clinical Study Actionable In a clinical study, three patients with lung adenocarcinoma harboring EGFR-RAD51 demonstrated partial responses as indicated by tumor regression, when treated with Tarceva (erlotinib) (PMID: 27102076). 27102076
EGFR-RAD51 Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR-RAD51 demonstrated sensitivity to treatment with Gilotrif (afatinib) in culture, resulting in decreased cell viability and inhibition of downstream MAPK and PI3K signaling (PMID: 27102076). 27102076
EGFR-RAD51 Advanced Solid Tumor sensitive Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR-RAD51 demonstrated sensitivity to treatment with Erbitux (cetuximab) in culture, resulting in decreased cell viability (PMID: 27102076). 27102076
EGFR-RAD51 Advanced Solid Tumor predicted - sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR-RAD51 demonstrated some sensitivity to treatment with Tagrisso (osimertinib) in culture, resulting in decreased cell viability (PMID: 27102076). 27102076
EGFR L861Q non-small cell lung carcinoma sensitive Afatinib FDA approved Actionable In a post-hoc analysis of Phase II and Phase III trials that supported FDA approval (LUX-Lung2, LUX-Lung 3, LUX-Lung 6), Gilotrif (afatinib) treatment resulted in an objective rate of 56.3% (9/16) in non-small cell lung cancer patients harboring EGFR L861Q (alone or in combination with EGFR L719X or exon 19 deletion), with a mean progression-free survival of 8.2 months, and an overall survival of 17.1 months (PMID: 26051236; NCT00525148, NCT00949650, and NCT01121393). 26051236
EGFR L861Q non-small cell lung carcinoma sensitive Afatinib Clinical Study Actionable In a prospective clinical study, Gilotrif (afatinib) treatment resulted in partial response in 33% (2/6), stable disease in 50% (3/6), and progressive disease in 17% (1/6) of non-small cell lung carcinoma patients harboring EGFR L861Q (PMID: 26354527). 26354527
EGFR L861Q non-small cell lung carcinoma sensitive Gefitinib Clinical Study Actionable In a retrospective analysis, a catalog of tyrosine kinase inhibitor responses of NSCLC patients harboring EGFR mutations determined that EGFR L861Q responded to Iressa (gefitinib), but possibly not as favorably as EGFR L858R, exon 19 deletion, and G719X mutations (PMID: 23344264). 23344264
EGFR L861Q esophagus squamous cell carcinoma resistant Cetuximab Preclinical Actionable In a preclinical study, esophageal squamous cell carcinoma cells harboring EGFR L861Q demonstrated resistance to treatment with Erbitux (cetuximab) in a cell viability assay (PMID: 27207775). 27207775
EGFR L861Q esophagus squamous cell carcinoma sensitive Afatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Gilotrif (afatinib) treatment resulted in apoptotic induction in esophagus squamous carcinoma cells harboring EGFR L861Q in culture and inhibited tumor growth in cell line xenograft models (PMID: 27207775). 27207775
EGFR L861Q non-small cell lung carcinoma sensitive Erlotinib Clinical Study Actionable In an analysis of published clinical data, non-small cell cancer patients harboring EGFR L861Q were demonstrated to respond to treatment with Tarceva (erlotinib), but possibly not as favorably as EGFR L858R, exon 19 deletion, and G719X mutations (PMID: 23344264). 23344264
EGFR L861Q non-small cell lung carcinoma decreased response Icotinib Clinical Study Actionable In a retrospective analysis, non-small cell lung cancer patients harboring EGFR L861Q demonstrated a response rate of 23.53% and disease control rate of 64.71%, and a median progression-free survival of 2.2 months following treatment with icotinib (J Clin Oncol 35, 2017 (suppl; abstr e14050)). detail...
EGFR L861Q esophagus squamous cell carcinoma resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, esophagus squamous cell carcinoma cells harboring EGFR L861Q demonstrated resistance to treatment with Tarceva (erlotinib) in a cell viability assay (PMID: 27207775). 27207775
EGFR G719S EGFR L861Q non-small cell lung carcinoma predicted - resistant Gefitinib Clinical Study Actionable In a clinical case study, Iressa (gefitinib) treatment resulted in disease progression within 2 months of treatment in a patient with non-small cell lung carcinoma harboring EGFR G719S and L861Q (PMID: 15897572). 15897572
EGFR D770_P772dup non-small cell lung carcinoma predicted - sensitive Poziotinib Phase II Actionable In a Phase II trial, treatment with Poziotinib (HM781-36B) resulted in objective partial responses in 64% (7/11) of patients with non-small cell lung cancer harboring EGFR exon 20 mutations, including a patient with EGFR D770_P772dup (reported as P772_H773insDNP) (PMID: 29686424; NCT03066206). 29686424
EGFR D770_P772dup non-small cell lung 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_P772dup achieved partial response (PMID: 30351341; NCT01854034). 30351341
EGFR S464L colorectal cancer sensitive MM-151 Preclinical Actionable In a preclinical study, MM-151 inhibited survival of colorectal cancer cell lines over expressing EGFR S464L in culture (PMID: 26843189). 26843189
EGFR S464L colorectal cancer resistant Panitumumab Preclinical Actionable In a preclinical study, colorectal cancer cell lines over expressing EGFR S464L were resistant to Vectibix (panitumumab)-induced growth inhibition in culture (PMID: 26843189). 26843189
EGFR S464L colorectal cancer resistant Cetuximab Preclinical Actionable In a preclinical study, colorectal cancer cell lines over expressing EGFR S464L were resistant to Erbitux (cetuximab)-induced growth inhibition in culture (PMID: 26843189). 26843189
EGFR G465R EGFR S464L colorectal cancer sensitive MM-151 Phase I Actionable In a Phase I trial, MM-151 treatment resulted in reduction of EGFR S464L and stabilization of EGFR G465R in circulating cell-free tumor DNA and prolonged stable disease in a colorectal cancer patient harboring both EGFR G465R and EGFR S464L (PMID: 26843189). 26843189
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 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 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 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 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 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 Clinical Study 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 transformed cells expressing EGFR L858R and T854A in culture (PMID: 19010870). 19010870
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 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 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 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 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 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 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 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 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 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 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 P741L Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR P741L were sensitive to treatment with Tagrisso (osimertinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR P741L Advanced Solid Tumor resistant CO1686 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR P741L were resistant to treatment with Rociletinib (CO-1686) in culture (PMID: 29141884). 29141884
EGFR P741L Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR P741L were sensitive to treatment with Gilotrif (afatinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR L62R Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR L62R were sensitive to treatment with Tagrisso (osimertinib) in culture (PMID: 29141884). 29141884
EGFR L62R Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR L62R were sensitive to treatment with Gilotrif (afatinib) in culture (PMID: 29141884). 29141884
EGFR L62R Advanced Solid Tumor sensitive Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR L62R were sensitive to treatment with Erbitux (cetuximab) in culture, demonstrating decreased cell viability (PMID: 29141884). 29141884
EGFR L62R Advanced Solid Tumor sensitive Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR L62R were sensitive to treatment with Tarceva (erlotinib) in culture (PMID: 29141884). 29141884
EGFR N771dup Advanced Solid Tumor resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR N771dup (reported as N771_P772insN) were resistant to treatment with Erbitux (cetuximab) in culture (PMID: 29141884). 29141884
EGFR N771dup Advanced Solid Tumor resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR N771dup (reported as N771_P772insN) were resistant to treatment with Tarceva (erlotinib) in culture (PMID: 29141884). 29141884
EGFR N771dup Advanced Solid Tumor resistant Gefitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR N771dup (reported as N771_P772insN) were resistant to treatment with Iressa (gefitinib) in culture (PMID: 29141884). 29141884
EGFR N771dup Advanced Solid Tumor resistant CO1686 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR N771dup (reported as N771_P772insN) were resistant to treatment with Rociletinib (CO-1686) in culture (PMID: 29141884). 29141884
EGFR N771dup Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR N771dup (reported as N771_P772insN) were sensitive to treatment with Tagrisso (osimertinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR L833F non-small cell lung carcinoma decreased response Icotinib Clinical Study Actionable In a retrospective analysis, non-small cell lung cancer patients harboring EGFR L833F demonstrated a response rate of 0% and disease control rate of 100%, and a median progression-free survival of 4.2 months following treatment with icotinib (J Clin Oncol 35, 2017 (suppl; abstr e14050)). detail...
EGFR R222C Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR R222C were sensitive to treatment with Gilotrif (afatinib) in culture (PMID: 29141884). 29141884
EGFR R222C Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR R222C were sensitive to treatment with Tagrisso (osimertinib) in culture (PMID: 29141884). 29141884
EGFR E709_T710delinsD EGFR L792F Advanced Solid Tumor sensitive Dacomitinib Preclinical - Cell culture Actionable In a preclinical study, Vizimpro (dacomitinib) inhibited growth of transformed cells expressing EGFR E709_T710delinsD and EGFR L792F in culture (PMID: 27913578). 27913578
EGFR E709_T710delinsD EGFR L792F Advanced Solid Tumor resistant Afatinib Preclinical - Cell culture Actionable In a preclinical study, acquisition of EGFR L792F was associated with resistance to Gilotrif in transformed cells expressing EGFR E709_T710delinsD in culture (PMID: 27913578). 27913578
EGFR E709_T710delinsD Advanced Solid Tumor sensitive Dacomitinib Preclinical Actionable In a preclinical study, transformed cells expressing EGFR E709_T710delinsD 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 E709_T710delinsD Advanced Solid Tumor decreased response Erlotinib Preclinical Actionable In a preclinical study, transformed cells expressing EGFR E709_T710delinsD demonstrated decreased sensitivity to first-generation EGFR inhibitors including Tarceva (erlotinib) in culture, when compared to second-generation inhibitors (PMID: 26206867). 26206867
EGFR E709_T710delinsD Advanced Solid Tumor sensitive Neratinib Preclinical Actionable In a preclinical study, transformed cells expressing EGFR E709_T710delinsD 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 E709_T710delinsD Advanced Solid Tumor decreased response Gefitinib Preclinical Actionable In a preclinical study, transformed cells expressing EGFR E709_T710delinsD demonstrated decreased sensitivity to the first-generation EGFR inhibitor Iressa (gefitinib) in culture, when compared to second-generation inhibitors, with an IC90 concentration approximately two-times the estimated trough concentration at the recommended dose (PMID: 26206867). 26206867
EGFR E709_T710delinsD Advanced Solid Tumor decreased response Osimertinib Preclinical Actionable In a preclinical study, transformed cells expressing EGFR E709_T710delinsD demonstrated decreased sensitivity to third-generation EGFR inhibitors including Tagrisso (AZD9291) in culture, when compared to second-generation inhibitors (PMID: 26206867). 26206867
EGFR E709_T710delinsD lung adenocarcinoma sensitive Afatinib Phase I Actionable In a clinical case study, treatment with Gilotrif (afatinib) in a lung adenocarcinoma patient harboring EGFR E709_T710delinsD resulted in tumor shrinkage, while prior treatment with Tarceva (erlotinib) had achieved stable disease (PMID: 26206867). 26206867
EGFR E709_T710delinsD Advanced Solid Tumor sensitive Afatinib Preclinical Actionable In a preclinical study, transformed cells expressing EGFR E709_T710delinsD 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 E709_T710delinsD Advanced Solid Tumor resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR E709_T710delinsD were resistant to treatment with Erbitux (cetuximab) in culture (PMID: 29141884). 29141884
EGFR E709_T710delinsD Advanced Solid Tumor decreased response CO1686 Preclinical Actionable In a preclinical study, transformed cells expressing EGFR E709_T710delinsD demonstrated decreased sensitivity to third-generation EGFR inhibitors including Rociletinib (CO-1686) in culture, when compared to second-generation inhibitors (PMID: 26206867). 26206867
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 E709V Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR E709V were sensitive to treatment with Tagrisso (osimertinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR E709V Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR E709V were sensitive to treatment with Gilotrif (afatinib) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR E709V Advanced Solid Tumor sensitive Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR E709V were sensitive to treatment with Erbitux (cetuximab) in culture, demonstrating reduced cell viability (PMID: 29141884). 29141884
EGFR E709V Advanced Solid Tumor resistant CO1686 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR E709V were resistant to treatment with Rociletinib (CO-1686) in culture (PMID: 29141884). 29141884
EGFR over exp PIK3CA E542K esophageal cancer sensitive Theliatinib Preclinical - Pdx Actionable In a preclinical study, Theliatinib treatment demonstrated decreased efficcacy in patient-derived xenograft (PDX) models of esophageal cancer with Egfr overexpression and PIK3CA E542K compared to models with only Egfr overexpression (PMID: 28881608). 28881608
EGFR over exp FGFR1 over exp esophageal cancer sensitive Theliatinib Preclinical - Pdx Actionable In a preclinical study, Theliatinib treatment demonstrated decreased efficcacy in patient-derived xenograft (PDX) models of esophageal cancer with both Egfr and Fgfr1 overexpression compared to models with only Egfr overexpression (PMID: 28881608). 28881608
EGFR over exp FGFR1 over exp esophageal cancer sensitive AZD4547 Preclinical - Pdx Actionable In a preclinical study, AZD4547 treatment resulted in tumor regression in patient-derived xenograft (PDX) models, with both Egfr and Fgfr1 overexpression (PMID: 28881608), 28881608
EGFR over exp FGFR1 amp head and neck squamous cell carcinoma sensitive AZD4547 + Gefitinib Preclinical - Cell culture Actionable In a preclinical study, head and neck squamous cell carcinoma cells harboring FGFR1 amplification and over expressing EGFR demonstrated sensitivity to the combination treatment of AZD4547 and Iressa (gefitinib) in culture, which also resulted in a synergistic effect (PMID: 26936917). 26936917
EGFR over exp FGFR1 amp head and neck squamous cell carcinoma resistant AZD4547 Preclinical - Cell culture Actionable In a preclinical study, head and neck squamous cell carcinoma cells with EGFR over expression and FGFR1 amplification demonstrated resistance to treatment with AZD4547 in culture (PMID: 26936917). 26936917
EGFR over exp KRAS wild-type pancreatic adenocarcinoma sensitive Afatinib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Gilotrif (afatinib) and Mekinist (trametinib) worked synergistically to inhibit growth of a pancreatic adenocarcinoma cell line with wild-type KRAS that demonstrated high EGFR expression and activation in culture (PMID: 28957417). 28957417
EGFR over exp KRAS wild-type pancreatic adenocarcinoma sensitive Trametinib + Triciribine Preclinical - Cell culture Actionable In a preclinical study, the combination of Triciribine (API-2) and Mekinist (trametinib) worked synergistically to inhibit growth of a pancreatic adenocarcinoma cell line with wild-type KRAS that demonstrated high EGFR expression and activation in culture (PMID: 28957417). 28957417
EGFR over exp FGFR2 amp head and neck squamous cell carcinoma resistant AZD4547 Preclinical - Cell culture Actionable In a preclinical study, head and neck squamous cell carcinoma cells harboring FGFR2 amplification and over expressing EGFR demonstrated resistance to treatment with AZD4547 in culture (PMID: 26936917). 26936917
EGFR over exp FGFR2 amp head and neck squamous cell carcinoma sensitive AZD4547 + Gefitinib Preclinical - Cell culture Actionable In a preclinical study, head and neck squamous cell carcinoma cells harboring FGFR2 amplification and over expressing EGFR demonstrated sensitivity to the combination treatment of AZD4547 and Iressa (gefitinib) in culture, which also resulted in a moderate synergistic effect (PMID: 26936917). 26936917
BRAF D594N BRAF G466A EGFR over exp MET over exp collecting duct carcinoma sensitive Capmatinib Preclinical - Pdx Actionable In a preclinical study, treatment with Capmatinib (INC280) inhibited tumor growth and reduced ERK signaling in a patient-derived xenograft (PDX) model derived from the ovarian metastasis of a patient with collecting duct carcinoma, which harbored BRAF D594N and BRAF G466A and had high levels of MET and EGFR expression (PMID: 28783719). 28783719
BRAF D594N BRAF G466A EGFR over exp MET over exp collecting duct carcinoma sensitive INC280 + Trametinib Preclinical - Pdx Actionable In a preclinical study, the combination of Mekinist (trametinib) and Capmatinib (INC280) induced tumor regression in a patient-derived xenograft (PDX) model derived from the ovarian metastasis of a patient with collecting duct carcinoma, which harbored BRAF D594N and BRAF G466A and had high levels of MET and EGFR expression (PMID: 28783719). 28783719
BRAF D594N BRAF G466A EGFR over exp MET over exp collecting duct carcinoma sensitive Trametinib Preclinical - Pdx Actionable In a preclinical study, treatment with Mekinist (trametinib) inhibited tumor growth and reduced ERK signaling in a patient-derived xenograft (PDX) model derived from the ovarian metastasis of a patient with collecting duct carcinoma, which harbored BRAF D594N and BRAF G466A and had high levels of MET and EGFR expression (PMID: 28783719). 28783719
BRAF V600E EGFR over exp colorectal cancer resistant Selumetinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, over expression of wild type EGFR in colorectal cancer cells harboring BRAF V600E resulted in sustained activation of Mapk signaling and resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E EGFR over exp colorectal cancer sensitive EBI-907 Preclinical - Cell culture Actionable In a preclinical study, EBI-907 inhibited growth of colorectal cancer cells harboring BRAF V600E and EGFR overexpression in culture (PMID: 26810733). 26810733
EGFR over exp lung squamous cell carcinoma sensitive Depatuxizumab mafodotin Preclinical - Cell line xenograft Actionable In a preclinical study, ABT-414 demonstrated cytoxicity against a lung squamous cell carcinoma cell line with EGFR over expression in culture and induced tumor regression in EGFR over expressing lung squamous cell carcinoma cell line xenograft models (PMID: 26846818). 26846818
EGFR over exp Advanced Solid Tumor predicted - 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 over exp squamous cell carcinoma sensitive GA201 Preclinical Actionable In a preclinical study, treatment with GA201 resulted in inhibition of EGFR signaling and induced antibody-dependent cell-mediated cytotoxicity towards EGFR-over expressing squamous cell carcinoma cells in culture (PMID: 23209031). 23209031
EGFR over exp lung cancer sensitive BGB-283 Preclinical - Cell culture Actionable In a preclinical study, BGB-283 inhibited proliferation of Egfr over expressing lung cancer cells in culture (PMID: 26208524). 26208524
EGFR over exp squamous cell carcinoma sensitive TAK-285 Preclinical - Cell line xenograft Actionable In a preclinical study, TAK-285 inhibited growth of squamous cell carcinoma cells harboring EGFR over expression in culture and in cell line xenograft models (PMID: 23983820). 23983820
EGFR over exp esophageal cancer sensitive Theliatinib Preclinical - Pdx Actionable In a preclinical study, Theliatinib treatment resulted in significant tumor growth inhibition in patient-derived xenograft (PDX) models of esophageal cancer with Egfr overexpression (PMID: 28881608) 28881608
EGFR over exp squamous cell carcinoma sensitive BGB-283 Preclinical - Cell line xenograft Actionable In a preclinical study, BGB-283 inhibited Egfr phosphorylation in Egfr over expressing squamous cell carcinoma cells in culture, and inhibited tumor growth in cell line xenograft models (PMID: 26208524). 26208524
EGFR over exp ERBB2 dec exp inflammatory breast carcinoma sensitive Sapitinib + Paclitaxel Preclinical - Pdx & cell culture Actionable In a preclinical study, combination of Sapatinib (AZD8931) and Taxol (paclitaxel) demonstrated enhanced antitumor activity in patient-derived, EGFR over expressing inflammatory breast cancer cell lines expressing low level of Erbb2 (Her2) protein in culture and in xenograft models (PMID: 24886365). 24886365
EGFR over exp ERBB2 dec exp inflammatory breast carcinoma sensitive Sapitinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Sapitinib (AZD8931) demonstrated antitumor activity in patient-derived, EGFR over expressing inflammatory breast cancer cell lines expressing low level of Erb2 (Her2) protein in culture and in xenograft models (PMID: 24886365). 24886365
EGFR-SEPT14 glioblastoma multiforme sensitive Erlotinib Preclinical - Cell line xenograft Actionable In a preclinical study, Tarceva (erlotinib) inhibited cell survival of a human glioblastoma multiforme cell line harboring an EGFR-SEPT14 fusion, and inhibited tumor growth in xenograft models (PMID: 23917401). 23917401
EGFR-SEPT14 glioblastoma multiforme sensitive Lapatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Tykerb (lapatinib) inhibited cell survival of a human glioblastoma multiforme cell line harboring an EGFR-SEPT14 fusion, and inhibited tumor growth in xenograft models (PMID: 23917401). 23917401
EGFR C797S EGFR L792H EGFR L858R Advanced Solid Tumor resistant Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EGFR C797S, EGFR L792H, and EGFR L858R were resistant to treatment with Tagrisso (osimertinib) in culture (PMID: 29702287). 29702287
EGFR C797S EGFR L792H EGFR L858R Advanced Solid Tumor resistant Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EGFR C797S, EGFR L792H, and EGFR L858R were resistant to treatment with Gilotrif (afatinib) in culture (PMID: 29702287). 29702287
EGFR C797S EGFR L792H EGFR L858R Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EGFR C797S, EGFR L792H, and EGFR L858R were resistant to treatment with Alunbrig (brigatinib) in culture (PMID: 29702287). 29702287
EGFR C797S EGFR L792H EGFR L858R Advanced Solid Tumor predicted - sensitive Gefitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EGFR C797S, EGFR L792H, and EGFR L858R demonstrated some efficacy to treatment with Iressa (gefitinib) in culture (PMID: 29702287). 29702287
EGFR A763_Y764insFQEA non-small cell lung carcinoma sensitive Erlotinib Clinical Study Actionable In contrast to other known exon 20 insertions, EGFR A763_Y764insFQEA is sensitive to tyrosine kinase inhibitors, such as Tarceva (erlotinib), in cells, in animal models and in NSCLC patients (PMID: 24353160). 24353160
EGFR A763_Y764insFQEA non-small cell lung carcinoma sensitive Erlotinib Clinical Study Actionable In a clinical study, a patient with non-small cell lung carcinoma harboring EGFR A763_Y764insFQEA demonstrated a partial response after treatment with Tarceva (erlotinib), however, another patient with the same mutation and tumor type demonstrated progressive disease when treated with Tarceva (erlotinib) (PMID: 28089594). 28089594
EGFR A763_Y764insFQEA non-small cell lung 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 A763_Y764insFQEA in culture (PMID: 29467275). 29467275
EGFR A763_Y764insFQEA non-small cell lung carcinoma sensitive Gefitinib Preclinical Actionable In a preclinical study, non-small cell lung cancer cells harboring EGFR A763_Y764insFQEA mutations demonstrated sensitivity to Iressa (gefitinib) in culture, in contrast to other Egfr exon 20 insertions, and consistent with clinical observations (PMID: 24353160). 24353160
EGFR A763_Y764insFQEA non-small cell lung carcinoma sensitive Gefitinib Clinical Study Actionable In a clinical study, a patient with non-small cell lung carcinoma harboring EGFR A763_Y764insFQEA demonstrated a partial response when treated with Iressa (gefitinib) (PMID: 28089594). 28089594
EGFR A763_Y764insFQEA non-small cell lung carcinoma sensitive Afatinib Preclinical Actionable In a preclinical study, non-small cell lung cancer cells harboring EGFR A763_Y764insFQEA mutations demonstrated sensitivity to Gilotrif (afatinib) in cell culture, in contrast to other EGFR exon 20 insertion mutations (PMID: 24353160). 24353160
EGFR A763_Y764insFQEA Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, Gilotrif (afatinib) inhibited EGFR signaling and proliferation of transformed cells expressing EGFR A763_Y764insFQEA in culture (PMID: 29467275, PMID: 29483211). 29483211 29467275
EGFR A763_Y764insFQEA Advanced Solid Tumor resistant CO1686 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A763_Y764insFQEA were resistant to treatment with Rociletinib (CO-1686) in culture (PMID: 29141884). 29141884
EGFR A763_Y764insFQEA non-small cell lung carcinoma sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, Tagrisso (osimertinib) inhibited growth of non-small cell lung cancer cells expressing EGFR A763_Y764insFQEA in culture (PMID: 29483211). 29483211
EGFR A763_Y764insFQEA Advanced Solid Tumor sensitive Naquotinib Preclinical - Cell culture Actionable In a preclinical study, Naquotinib (ASP8273) inhibited EGFR signaling and proliferation of transformed cells expressing EGFR A763_Y764insFQEA in culture (PMID: 29467275). 29467275
EGFR A763_Y764insFQEA Advanced Solid Tumor sensitive Erlotinib Preclinical - Cell culture Actionable In a preclinical study, Tarceva (erlotinib) inhibited EGFR signaling and proliferation of transformed cells expressing EGFR A763_Y764insFQEA in culture (PMID: 29467275). 29483211 29467275
EGFR A763_Y764insFQEA Advanced Solid Tumor sensitive Poziotinib Preclinical - Cell culture Actionable In a preclinical study, Poziotinib (HM781-36B) inhibited EGFR phosphorylation and growth of a transformed cell line expressing EGFR A763_Y764insFQEA in culture (PMID: 29686424). 29686424
EGFR A763_Y764insFQEA Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, Tagrisso (osimertinib) inhibited EGFR signaling and proliferation of transformed cells expressing EGFR A763_Y764insFQEA in culture (PMID: 29467275). 29467275
EGFR A763_Y764insFQEA non-small cell lung 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 a patient harboring EGFR A763_Y764insFQEA achieved stable disease (PMID: 30351341; NCT01854034). 30351341
EGFR A763_Y764insFQEA Advanced Solid Tumor resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR A763_Y764insFQEA were resistant to treatment with Erbitux (cetuximab) in culture (PMID: 29141884). 29141884
EGFR A763_Y764insFQEA Advanced Solid Tumor predicted - sensitive TAS6417 Preclinical - Cell culture Actionable In a preclinical study, TAS6417 inhibited EGFR phosphorylation and proliferation of cells expressing EGFR exon 20 insertion mutations, including EGFR A763_Y764insFQEA, in culture (PMID: 29748209). 29748209
EGFR A750P EGFR L747_E749del non-small cell lung carcinoma sensitive WZ4002 + Trametinib 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 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 non-small cell lung 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 V769M Advanced Solid Tumor resistant CO1686 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 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 H773dup non-small cell lung carcinoma resistant Afatinib Preclinical Actionable In a preclinical study, non-small cell carcinoma cell lines harboring EGFR exon 20 insertions, including EGFR H773dup (reported as H773_V774insH), demonstrated resistance to Gilotrif (afatinib) in cell culture (PMID: 24353160). 24353160
EGFR H773dup non-small cell lung carcinoma resistant Erlotinib Clinical Study Actionable In a retrospective analysis, non-small cell lung cancer patients harboring EGFR exon 20 insertions, such as EGFR H773dup (reported as H773_V774insH), displayed progressive disease following treatment with Tarceva (erlotinib), and resistance to Tarceva (erlotinib) was replicated in cell culture studies (PMID: 24353160). 24353160
EGFR H773dup Advanced Solid Tumor resistant Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR H773dup (reported as H773_V774insH) were resistant to treatment with Gilotrif (afatinib) in culture (PMID: 29141884). 29141884
EGFR H773dup non-small cell lung 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, resulted in partial response in a patient harboring EGFR H773dup (PMID: 30351341; NCT01854034). 30351341
EGFR H773dup Advanced Solid Tumor resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR H773dup (reported as H773_V774insH) were resistant to treatment with Tarceva (erlotinib) in culture (PMID: 29141884). 29141884
EGFR H773dup Advanced Solid Tumor resistant Gefitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EGFR H773dup (reported as H773_V774insH) were resistant to treatment with Iressa (gefitinib) in culture (PMID: 29141884). 29141884
EGFR H773dup non-small cell lung carcinoma resistant Gefitinib Clinical Study Actionable In a retrospective analysis, non-small cell lung cancer patients harboring EGFR exon 20 insertions, such as EGFR H773dup (reported as H773_V774insH), displayed progressive disease following treatment with Iressa (gefitinib) (PMID: 24353160). 24353160
EGFR exon 19 del EGFR S645C lung adenocarcinoma resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, expression of EGFR S645C in lung adenocarcinoma cells harboring EGFR exon 19 deletion mutations led to resistance to Tarceva (erlotinib) in culture (PMID: 27478040). 27478040
EGFR E804G EGFR P699L lung adenocarcinoma predicted - resistant Gefitinib Clinical Study 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 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 mut MET amp non-small cell lung carcinoma sensitive Capmatinib + Gefitinib Phase Ib/II Actionable In a Phase Ib/II trial, Capmatinib (INC280) and Iressa (gefitinib) combination treatment resulted in an objective response rate of 27% (43/161) in non-small cell lung cancer patients harboring EGFR mutations and MET dysregulation (amplification or overexpression), with an objective response rate of 47% in Phase II patients with a MET gene copy number greater than 6 (PMID: 30156984). 30156984
EGFR mut MET amp lung adenocarcinoma resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, amplification of MET was identified in a lung adenocarcinoma cell line harboring EGFR mutation that acquired resistance to Tarceva (erlotinib) in culture (PMID: 28630215). 28630215
EGFR mut MET amp lung adenocarcinoma sensitive Erlotinib + EMD 1214063 Preclinical - Cell culture Actionable In a preclinical study, Tarceva (erlotinib) and EMD 1214063 synergistically inhibited growth of lung carcinoma cells harboring EGFR mutation and Met amplification in culture (PMID: 28630215). 28630215
EGFR mut MET amp non-small cell lung carcinoma predicted - sensitive Crizotinib Clinical Study Actionable In a clinical study, Xalkori (crizotinib) treatment resulted in partial response (PR) in 50% (4/8) of patients with EGFR mutant non-small cell lung cancer that acquired MET amplification after EGFR TKI therapy, although the response was short-lived, with a median progression-free survival of 3.5 months in patients achieved PR (PMID: 30268451). 30268451
EGFR mut TP53 mut non-small cell lung carcinoma decreased response unspecified EGFR tyrosine kinase inhibitor Clinical Study Actionable In a clinical study, non-small cell lung cancer patients harboring both EGFR and TP53 mutations demonstrated a disease control rate of 70.3% (26/37) following first-line treatment with an EGFR inhibitor such as Iressa (gefitinib), Tarceva (erlotinib), Gilotrif (afatinib), or Dacomitinib, compared to a DCR of 88.2% (75/85) in TP53 wild-type, EGFR-mutant patients (PMID: 27780855). detail... 27780855
EGFR mut TP53 exon 8 non-small cell lung carcinoma decreased response unspecified EGFR tyrosine kinase inhibitor Clinical Study Actionable In a clinical study, EGFR-mutant non-small cell lung cancer patients with TP53 exon 8 mutations demonstrated a disease control rate (DCR) of 42% (5/12), median progression-free survival (mPFS) of 4.2 mo and median overall survival (mOS) of 16.2 mo with first-line EGFR tyrosine kinase inhibitor treatment (such as Iressa (gefitinib), Tarceva (erlotinib), Gilotrif (afatinib), or Dacomitinib), vs a DCR of 87% (97/111), mPFS of 12.5 mo, and mOS of 32.3 mo in TP53 exon 8 wild-type patients (PMID: 27780855). detail... 27780855
EGFR mutant non-small cell lung carcinoma sensitive Sorafenib Phase III Actionable In a Phase III trial, treatment with Nexavar (sorafenib) in non-small cell lung cancer patients harboring an EGFR mutation resulted in a greater overall survival and progression free survival when compared to placebo (PMID: 26743856). 26743856
EGFR mutant lung cancer sensitive CO1686 Preclinical - Cell line xenograft Actionable In a preclinical study, Rociletinib (CO-1686) induced tumor regression in EGFR-mutant human non-small cell lung cancer cell line xenograft models, while slightly inhibiting tumor growth in xenograft models of a wild-type EGFR human squamous carcinoma cell line (PMID: 24065731). 24065731
EGFR mutant Advanced Solid Tumor no benefit N/A Clinical Study Emerging In a clinical study, 87.5% (7/8) of solid tumor patients harboring EGFR alterations experienced disease progression within 2 months of anti-PD1/PD-L1 monotherapy, indicating a risk for hyperprogression on immunotherapy (PMID: 28351930). 28351930
EGFR mutant non-small cell lung carcinoma predicted - sensitive BMS-690514 Phase II Actionable In a Phase IIa clinical trial, BMS-690514 demonstrated safety and preliminary anti-tumor activity in patients with non-small cell lung cancer, with patients harboring EGFR mutations achieving a disease control rate (DCR) of 70% (7/10), compared to a DCR of 29% (6/21) in EGFR-wild type patients (PMID: 23490650). 23490650
EGFR mutant non-small cell lung carcinoma sensitive Osimertinib Guideline Actionable Tagrisso (osimertinib) is included in guidelines for patients with EGFR mutant non-small cell lung cancer who have progressive leptomeningeal disease (NCCN.org). detail...
EGFR mutant non-small cell lung carcinoma predicted - sensitive Afatinib Clinical Study Actionable In a prospective clinical study, Gilotrif (afatinib) treatment resulted in partial response in 22% (22/58), stable disease in 47% (27/58), and progressive disease in 31% (18/58) of non-small cell lung carcinoma patients carrying an EGFR mutation (PMID: 26354527). 26354527
EGFR mutant non-small cell lung carcinoma decreased response Pembrolizumab Clinical Study Actionable In a retrospective study, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Durvalumab (MEDI4736), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694). 27225694
EGFR mutant lung adenocarcinoma not applicable N/A Clinical Study Emerging In a clinical study, lung adenocarcinoma patients with compound EGFR mutations had inferior overall survival when compared to patients with single EGFR mutations (PMID: 26785607), suggesting that the presence of compound EGFR mutations may be have prognostic significance in lung adenocarcinoma. 26785607
EGFR mutant non-small cell lung carcinoma decreased response Durvalumab Clinical Study Actionable In a retrospective study, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Imfinzi (durvalumab), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694). 27225694
EGFR mutant non-small cell lung carcinoma sensitive Pelitinib Phase I Actionable In a Phase I study, Pelitinib (EKB-569) demonstrated efficacy in 2 patients with non-small cell lung cancer with EGFR mutations and acquired resistance to gefitinib (PMID: 16364494). 16364494
EGFR mutant non-small cell lung carcinoma decreased response Atezolizumab Clinical Study Actionable In a retrospective study, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Durvalumab (MEDI4736), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694). 27225694
EGFR mutant non-small cell lung carcinoma predicted - sensitive DS-1205b + Erlotinib Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with the combination of DS-1205b and Tarceva (erlotinib) delayed the onset of therapeutic resistance compared to Tarceva (erlotinib) alone in an EGFR-mutant non-small cell lung cancer cell line xenograft model, and overcame resistance to Tarceva (erlotinib) in a Tarceva (erlotinib)-resistant xenograft model (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #395P). detail...
EGFR mutant non-small cell lung carcinoma predicted - sensitive NGI-1 Preclinical - Cell culture Actionable In a preclinical study, NGI-1 inhibited EGFR phosphorylation and proliferation and induced cell cycle arrest in non-small cell lung cancer cell lines harboring kinase domain mutations in EGFR in culture (PMID: 27694802). 27694802
EGFR mutant non-small cell lung carcinoma decreased response Nivolumab Clinical Study Actionable In a retrospective study, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Durvalumab (MEDI4736), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694). 27225694
EGFR mutant non-small cell lung 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=0.51), overall survival (HR=0.46), and objective response (odd ratio=3.34) in non-small cell lung cancer patients harboring EGFR mutations compared to the overall study population (PMID: 25057173; NCT00312377). 25057173
EGFR mutant non-small cell lung carcinoma predicted - sensitive DS-1205b + Osimertinib Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with the combination of DS-1205b and Tagrisso (osimertinib) delayed the onset of therapeutic resistance compared to Tagrisso (osimertinib) alone in an EGFR-mutant non-small cell lung cancer cell line xenograft model (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #395P). detail...