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Gene Symbol ERBB2
Synonyms CD340 | HER-2 | HER-2/neu | HER2 | MLN 19 | NEU | NGL | TKR1
Gene Description ERBB2 (HER2), erb-b2 receptor tyrosine kinase 2, is an EGFR receptor tyrosine kinase that activates PI3K-AKT-mTOR and RAS-RAF-MEK-ERK pathways, therefore regulating growth and transformation (PMID: 17471238). ERBB2 (HER2) amplification, overexpression, and activation has been implicated in several tumor types (PMID: 17471238).

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
A1216D missense no effect - predicted ERBB2 (HER2) A1216D lies within the cytoplasmic domain of the Erbb2 (Her2) protein (UniProt.org). A1216D has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, is predicted to have no effect on Erbb2 (Her2) protein function.
A293T missense no effect - predicted ERBB2 (HER2) A293T lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). A293T has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, is predicted to have no effect on Erbb2 (Her2) protein function.
A386D missense unknown ERBB2 (HER2) A386D lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). A386D has been identified in sequencing studies (PMID: 24728327), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
A440T missense unknown ERBB2 (HER2) A440T lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). A440T induces increased cell proliferation and cell viability as compared to wild-type Erbb2 (Her2) in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
A751T missense unknown ERBB2 (HER2) A751T lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). A751T results in decreased cell proliferation and cell viability as compared to wild-type Erbb2 (Her2) in one of two cell lines (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown.
A771_Y772insAYVM insertion gain of function - predicted ERBB2 (HER2) A771_Y772insAYVM results in the insertion of a four amino acids in the protein kinase domain of the Erbb2 (Her2) protein between amino acids 771 and 772 (UniProt.org). A771_Y772insAYVM has not been characterized, however other exon 20 insertions are activating thus, A771_Y772insAYVM is predicted to lead to gain of Erbb2 (Her2) function (PMID: 16843263, PMID: 17311002, PMID: 23220880).
A775_G776insIRDG insertion no effect - predicted ERBB2 (HER2) A775_G776insIRDG results in the insertion of four amino acids in the protein kinase domain of the Erbb2 (Her2) protein between amino acids 775 and 776 (UniProt.org). A775_G776insIRDG has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, is predicted to have no effect on Erbb2 (Her2) protein function.
A775_G776insSVMA insertion gain of function - predicted ERBB2 (HER2) A775_G776insSVMA results in the insertion of four amino acids in the protein kinase domain of the Erbb2 (Her2) protein between amino acids 775 and 776 (UniProt.org). A775_G776insSVMA has not been characterized however, because similar exon 20 insertion mutations are activating (PMID: 17311002), A775_G776insSVMA is predicted to lead to activation of Erbb2 (Her2).
A775_G776insYVMA insertion gain of function ERBB2 (HER2) A775_G776insYVMA results in the insertion of four amino acids in the protein kinase domain of the Erbb2 (Her2) protein between amino acids 775 and 776 (UniProt.org). A775_G776insYVMA results in the same amino acid change as M774_A775insAYVM, which leads to constitutive phosphorylation of Erbb2 (Her2) and is transforming in cell culture (PMID: 17311002, PMID: 29967253).
A890V missense unknown ERBB2 (HER2) A890V lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). A890V has been identified in sequencing studies (PMID: 22722839), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
act mut unknown gain of function ERBB2 (HER2) act mut indicates that this variant results in a gain of function in the Erbb2 (Her2) protein. However, the specific amino acid change has not been identified.
amp none no effect ERBB2 (HER2) amplification indicates an increased number of copies of the ERBB2 (HER2) gene. However, the mechanism causing the increase is unspecified.
C311R missense gain of function ERBB2 (HER2) C311R lies within the extracellular domain of the Erbb2 (Her2) protein (PMID: 22908275). C311R results in disulfide bond-mediated Erbb2 (Her2) dimerization and is transforming in cell culture (PMID: 22908275).
C334S missense gain of function ERBB2 (HER2) C334S lies within the extracellular domain of the Erbb2 (Her2) protein (PMID: 22908275). C334S results in disulfide bond-mediated Erbb2 (Her2) dimerization and is transforming in cell culture (PMID: 22908275).
C544F missense unknown ERBB2 (HER2) C544F lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). C544F has been identified in sequencing studies (PMID: 29420467), but has not been biochemically chatacterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
C630Y missense unknown ERBB2 (HER2) C630Y lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). C630Y has been identified in the scientific literature (PMID: 18413839), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
C805S missense unknown ERBB2 (HER2) C805S lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). C805S is associated with resistance to Erbb2 (Her2)-targeted therapies in cell culture (PMID: 28363995), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019). Y
D1058A missense no effect - predicted ERBB2 (HER2) D1058A lies within the cytoplasmic domain of the Erbb2 (Her2) protein (UniProt.org). D1058A has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, is predicted to have no effect on Erbb2 (Her2) protein function.
D1144Y missense no effect - predicted ERBB2 (HER2) D1144Y lies within the cytoplasmic domain of the Erbb2 (Her2) protein (UniProt.org). D1144Y has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, is predicted to have no effect on Erbb2 (Her2) protein function.
D251N missense unknown ERBB2 (HER2) D251N lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). D251N has not been characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
D277G missense unknown ERBB2 (HER2) D277G lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). D277G has been identified in sequencing studies (PMID: 29420467), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
D277H missense unknown ERBB2 (HER2) D277H lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). D277H results in minor changes in Erbb2 (Her2) activity alone, but enhanced phosphorylation of Erbb2 (Her2), Shc and Erk when in combination with S310F in cell culture (PMID: 24971884), and therefore, its effect on Erbb2 (Her2) protein function is unknown.
D277Y missense no effect - predicted ERBB2 (HER2) D277Y lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). D277Y did not demonstrate Erbb2 (Her2) gain of function activity in a cell culture assay (J Clin Oncol 35, 2017 (suppl; abstr e23150)) and therefore, is predicted to have no effect on Erbb2 (Her2) protein function.
D326G missense no effect ERBB2 (HER2) D326G lies within the extracellular domain of the Erbb2 (Her2) protein (PMID: 22908275). D326G does not result in increased Erbb2 (Her2) phosphorylation or the ability to transform cells in culture (PMID: 22908275).
D417Y missense unknown ERBB2 (HER2) D417Y lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). D417Y results in decreased cell proliferation and cell viability as compared to wild-type Erbb2 (Her2) in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
D582N missense no effect - predicted ERBB2 (HER2) D582N lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). D582N has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, is predicted to have no effect on Erbb2 (Her2) protein function.
D742H missense no effect - predicted ERBB2 (HER2) D742H lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). D742H has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, is predicted to have no effect on Erbb2 (Her2) protein function.
D769A missense loss of function - predicted ERBB2 (HER2) D769A lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). D769A is predicted to confer a loss of function to the Erbb2 (Her2) protein as indicated by loss of Erbb2 (Her2) kinase activity (PMID: 23843458).
D769H missense unknown ERBB2 (HER2) D769H lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). D769H confers resistance to selected tyrosine kinase inhibitors (PMID: 31588020), results in constitutive phosphorylation of Erbb2 (Her2), activation of downstream signaling, is transforming in cell culture (PMID: 29967253, PMID: 31588020), and promotes tumor formation in xenograft models (PMID: 23220880), however, in another study, induces similar cell proliferation and cell viability to wild-type Erbb2 (Her2) in two different cell lines (PMID: 29533785), and therefore, its effect on Erbb2 (Her2) protein function is unknown. Y
D769N missense unknown ERBB2 (HER2) D769N lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). D769N confers resistance to selected tyrosine kinase inhibitors, results in activation of Erbb2 (Her2) downstream signaling, and is transforming in culture in one study (PMID: 31588020), but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) in another study (PMID: 29533785), and therefore, its effect on Erbb2 (Her2) protein function is unknown. Y
D769Y missense gain of function ERBB2 (HER2) D769Y lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). D769Y results in constitutive phosphorylation of Erbb2 (Her2), increased downstream signaling, is transforming in cell culture (PMID: 23220880, PMID: 29967253, PMID: 31588020), and confers resistance to selected tyrosine kinase inhibitors (PMID: 31588020). Y
D821N missense gain of function - predicted ERBB2 (HER2) D821N lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). D821N is weakly transforming and confers resistance to the Erbb2 (Her2) inhibitor Tykerb (lapatinib) in cell culture (PMID: 18413839) and therefore, is predicted to result in a gain of Erbb2 (Her2) protein function. Y
D845A missense loss of function ERBB2 (HER2) D845A lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). D845A results in loss of Erbb2 (Her2) phosphorylation and abolishes transformation potential in cell culture (PMID: 22908275).
D880N missense no effect - predicted ERBB2 (HER2) D880N lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). D880N has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, is predicted to have no effect on Erbb2 (Her2) protein function.
dec exp none no effect ERBB2 (HER2) dec exp indicates decreased expression of the Erbb3 (Her3) protein and/or mRNA. However, the mechanism causing the decreased expression is unspecified.
E1021Q missense no effect - predicted ERBB2 (HER2) E1021Q lies within the cytoplasmic domain of the Erbb2 (Her2) protein (UniProt.org). E1021Q has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, is predicted to have no effect on Erbb2 (Her2) protein function.
E1064Q missense no effect - predicted ERBB2 (HER2) E1064Q lies within the cytoplasmic domain of the Erbb2 (Her2) protein (UniProt.org). E1064Q has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, is predicted to have no effect on Erbb2 (Her2) protein function.
E1229* nonsense unknown ERBB2 (HER2) E1229* results in a premature truncation of the Erbb2 (Her2) protein at amino acid 1229 of 1255 (UniProt.org). E1229* has not been characterized in the scientific literature and therefore, its effect on Erbb2 (Her2) function is unknown (PubMed, Oct 2019).
E1244D missense no effect - predicted ERBB2 (HER2) E1244D lies within the cytoplasmic domain of the Erbb2 (Her2) protein (UniProt.org). E1244D has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, is predicted to have no effect on Erbb2 (Her2) protein function.
E1244Q missense no effect - predicted ERBB2 (HER2) E1244Q lies within the cytoplasmic domain of the Erbb2 (Her2) protein (UniProt.org). E1244Q has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
E265K missense unknown ERBB2 (HER2) E265K lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). E265K has been identified in sequencing studies (PMID: 24997986, PMID: 29338072), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
E280K missense no effect - predicted ERBB2 (HER2) E280K lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). E280K has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785)and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
E321G missense gain of function ERBB2 (HER2) E321G lies within the extracellular domain of the Erbb2 (Her2) protein (PMID: 22908275). E321G results in disulfide bond-mediated Erbb2 (Her2) dimerization and is transforming in cell culture (PMID: 22908275, PMID: 29533785).
E693K missense gain of function - predicted ERBB2 (HER2) E693K lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). E693K results in increased cell survival as compared to wild-type Erbb2 (Her2) in culture (PMID: 30449325), and therefore, is predicted to result in a gain of Erbb2 (Her2) protein function.
E717D missense gain of function ERBB2 (HER2) E717D lies within the cytoplasmic domain of the Erbb2 (Her2) protein (UniProt.org). E717D confers a gain of function to the Erbb2 (Her2) protein as indicated by increased phosphorylation of Erbb2 (Her2), downstream signaling, and colony formation, and is transforming in cell culture (PMID: 31046123).
E717K missense unknown ERBB2 (HER2) E717K lies within the cytoplasmic domain of the Erbb2 (Her2) protein (UniProt.org). E717K has been demonstrated to confer resistance to Tykerb (lapatinib) in cell culture (PMID: 18413839), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019). Y
E719G missense unknown ERBB2 (HER2) E719G lies within the cytoplasmic domain of the Erbb2 (Her2) protein (UniProt.org). E719G is associated with drug resistance in cell culture (PMID: 18413839), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019). Y
E719K missense unknown ERBB2 (HER2) E719K lies within the cytoplasmic domain of the Erbb2 (Her2) protein (UniProt.org). E719K has identified in the scientific literature (PMID: 18413839), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
E757A missense unknown ERBB2 (HER2) E757A lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). E757A has not been characterized in the scientific literature and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
E812K missense unknown ERBB2 (HER2) E812K lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). E812K confers Tykerb (lapatinib) resistance in cell culture (PMID: 18413839), but has not been biochemically characterized, and therefore its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019). Y
E930D missense no effect - predicted ERBB2 (HER2) E930D lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). E930D has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
E930K missense no effect - predicted ERBB2 (HER2) E930K lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). E930K has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
E971G missense unknown ERBB2 (HER2) E971G lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). E971G has been identified in sequencing studies (PMID: 21347793), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Sep 2019).
ERBB2 - TMEM98 fusion unknown ERBB2-TMEM98 results from the fusion of ERBB2 (HER2) and TMEM98. ERBB2-TMEM98 has not been characterized in the scientific literature and therefore, its effect on protein function is unknown (PubMed, Oct 2019).
exon 20 ins insertion gain of function - predicted ERBB2 (HER2) exon 20 insertions are in-frame insertions within the kinase domain of Erbb2 (Her2) (PMID: 16843263). Exon 20 insertions result in increased Erbb2 (Her2) kinase activity, and are associated with low sensitivity to Egfr tyrosine kinase inhibitors (PMID: 16843263) and therefore, is predict to result in a gain of Erbb2 (Her2) protein function.
exon20 unknown unknown ERBB2 (HER2) exon 20 indicates an unspecified mutation has occurred in exon 20 of the ERBB2 (HER2) gene.
F616L missense unknown ERBB2 (HER2) F616L lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). F616L has not been characterized in the scientific literature and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
fusion fusion unknown ERBB2 (HER2) fusion indicates a fusion of the ERBB2 (HER2) gene, but the fusion partner is unknown.
G1015E missense unknown ERBB2 (HER2) G1015E lies within the cytoplasmic domain of the Erbb2 (Her2) protein (UniProt.org). G1015E has been identified in sequencing studies (PMID: 25925381), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
G1015W missense no effect - predicted ERBB2 (HER2) G1015W lies within the cytoplasmic domain of the Erbb2 (Her2) protein (UniProt.org). G1015W has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
G1041fs frameshift unknown ERBB2 (HER2) G1041fs results in a change in the amino acid sequence of the Erbb2 (Her2) protein beginning at aa 1041 of 1255, likely resulting in premature truncation of the functional protein (UniProt.org). G1041fs has not been characterized in the scientific literature and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
G222C missense unknown ERBB2 (HER2) G222C lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). G222C results in increased transformation ability as compared to wild-type Erbb2 (Her2) in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
G292R missense gain of function - predicted ERBB2 (HER2) G292R lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). G292R results in increased cell growth in culture (PMID: 24997986) and therefore, is predicted to lead to a gain of Erbb2 (Her2) protein function.
G309A missense unknown ERBB2 (HER2) G309A lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). G309A does not result in increased Erbb2 (Her2) phosphorylation, but is transforming in cell culture and promotes tumor formation in xenograft models, and is predicted to enhance Erbb2 (Her2) dimerization in one study (PMID: 23220880), however, in another study, G309A results in similar cell proliferation and viability levels to wild-type Erbb2 (Her2) in two different cell lines in culture (PMID: 29533785), and therefore, its effect on Erbb2 (Her2) protein function is unknown.
G309E missense unknown ERBB2 (HER2) G309E lies within the extracellular domain of the Erbb2 (Her2) protein (PMID: 22908275). G309E results in disulfide bond-mediated Erbb2 (Her2) dimerization and is transforming in cell culture in one study (PMID: 22908275), but in another study, G309E results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) in two different cell lines in culture (PMID: 29533785), and therefore, its effect on Erbb2 (Her2) protein function is unknown.
G383E missense no effect - predicted ERBB2 (HER2) G383E lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). G383E has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
G660D missense gain of function ERBB2 (HER2) G660D lies within the transmembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). G660D leads to constitutive activation of Erbb2 (Her2) and increased downstream signaling in cell culture (PMID: 26545934) and results in increased cell survival and the formation of multi-acinar bodies in the absence of ligand (PMID: 30449325).
G660R missense gain of function ERBB2 (HER2) G660R lies within the transmembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). G660R results in elevated Erbb2 (Her2) phosphorylation in vitro and increased cell survival as compared to wild-type Erbb2 (Her2) in culture (PMID: 30449325).
G776C missense unknown ERBB2 (HER2) G776C lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). G776C has been identified in the scientific literature (PMID: 22761469), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Feb 2020).
G776delinsLC indel gain of function ERBB2 (HER2) G776delinsLC results in a deletion of a glycine (G) at amino acid 776 within the protein kinase domain of the Erbb2 (Her2) protein, combined with the insertion of a leucine (L) and a cystine (C) at the same site (UniProt.org). G776delinsLC leads to constitutive activation of Erbb2 (Her2), increased downstream signaling, is transforming in cell culture (PMID: 26545934, PMID: 29967253, PMID: 31588020), and confers resistance to selected tyrosine kinase inhibitors (PMID: 31588020). Y
G776delinsVC indel gain of function ERBB2 (HER2) G776delinsVC results in a deletion of a glycine (G) at amino acid 776 within the protein kinase domain of the Erbb2 (Her2) protein, combined with the insertion of a valine (V) and a cystine (C) at the same site (UniProt.org). G776delinsVC leads to constitutive activation of Erbb2 (Her2), increased downstream signaling (PMID: 26545934, PMID: 31588020), is transforming in cell culture (PMID: 29533785, PMID: 29967253), and confers resistance to selected tyrosine kinase inhibitors (PMID: 31588020). Y
G776delinsVV indel gain of function ERBB2 (HER2) G776delinsVV results in a deletion of a glycine (G) at amino acid 776 within the protein kinase domain of the Erbb2 (Her2) protein, combined with the insertion of two valines (V) at the same site (UniProt.org). G776delinsVV results in constitutive ERbb2 (Her2) phosphorylation, activation of downstream signaling, is transforming in cell culture (PMID: 29686424, PMID: 31588020), and confers resistance to selected tyrosine kinase inhibitors (PMID: 31588020). Y
G776S missense gain of function ERBB2 (HER2) G776S lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). G776S results in increased Erbb2 (Her2) kinase activity, activation of the Mapk pathway (PMID: 18039657), is transforming in cell culture (PMID: 29967253), and in one of two cell lines, G776S increased cell proliferation and cell viability as compared to wild-type Erbb2 (Her2) (PMID: 29533785).
G776V missense gain of function ERBB2 (HER2) G776V lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). G776V confers a gain of function to the Erbb2 (Her2) protein as indicated by increased downstream Mapk signaling and colony formation (Chudnovsky,Y et al. JCO Prec Onc, Aug 2017), transformation in cell culture (PMID: 29967253), and increased cell proliferation and cell viability as compared to wild-type Erbb2 (Her2) in one of two cell lines (PMID: 29533785).
G776_V777insVC insertion gain of function - predicted ERBB2 (HER2) G776_V777insVC results in the insertion of two amino acids in the protein kinase domain of the Erbb2 (Her2) protein between amino acids 776 and 777 (UniProt.org). G776_V777insVC has not been biochemically characterized, however, other Erbb2 (Her2) exon 20 insertions are activating (PMID: 16843263, PMID: 17311002, PMID: 23220880), and therefore, G776_V777insVC is predicted to lead to gain of Erbb2 (Her2) function.
G776_V777insVGC insertion gain of function - predicted ERBB2 (HER2) G776_V777insVGC results in the insertion of three amino acids in the protein kinase domain of the Erbb2 (Her2) protein between amino acids 776 and 777 (UniProt.org). G776_V777insVGC has not been characterized, however other exon 20 insertions are activating thus, G776_V777insVGC is predicted to lead to gain of Erbb2 (Her2) function (PMID: 16843263, PMID: 17311002, PMID: 23220880).
G776_V777insYVMA insertion gain of function ERBB2 (HER2) G776_V777insYVMA results in the insertion of four amino acids in the protein kinase domain of the Erbb2 (Her2) protein between amino acids 776 and 777 (UniProt.org). G776_V777insYVMA results in constitutive phosphorylation of Erbb2 (Her2), activation of downstream signaling, and is transforming in cell culture (PMID: 16843263).
G778A missense unknown ERBB2 (HER2) G778A lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). G778A has been identified in the scientific literature (PMID: 29420467), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
G778_P780dup duplication gain of function ERBB2 (HER2) G778_P780dup (also referred to as P780_Y781insGSP and V777_G778insGSP) indicates the insertion of 3 duplicate amino acids, glycine (G)-778 through proline (P)-781, in the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). G778_P780dup results in constitutive activation of Erbb2 (Her2), increased downstream signaling, is transforming in cell culture (PMID: 23220880, PMID: 31588020), and confers resistance to selected tyrosine kinase inhibitors (PMID: 31588020). Y
G778_S779insCPG insertion gain of function - predicted ERBB2 (HER2) G778_S779insCPG results in the insertion of three amino acids in the protein kinase domain of the Erbb2 (Her2) protein between amino acids 778 and 779 (UniProt.org). G778_S779insCPG is transforming in culture (PMID: 28363995), and based on the effects of other ERBB2 (HER2) exon 20 insertions (PMID: 16843263, PMID: 17311002), is predicted to result in a gain of Erbb2 (Her2) function.
G778_S779insG insertion gain of function - predicted ERBB2 (HER2) G778_S779insG results in the insertion of a glycine (G) in the protein kinase domain of the Erbb2 (Her2) protein between amino acids 778 and 779 (UniProt.org). G778_S779insG has not been characterized, however other exon 20 insertions are activating thus, G778_S779insG is predicted to lead to gain of Erbb2 (Her2) function (PMID: 16843263, PMID: 17311002, PMID: 23220880) and has been demonstrated to be transforming in cell culture (PMID: 29967253).
G778_S779insLPS insertion gain of function ERBB2 (HER2) G778_S779insLPS results in the insertion of three amino acids in the protein kinase domain of the Erbb2 (Her2) protein between amino acids 778 and 779 (UniProt.org). G778_S779insLPS results in constitutive phosphorylation of Erbb2 (Her2), activation of downstream signaling, is transforming in cell culture, and confers resistance to selected tyrosine kinase inhibitors (PMID: 31588020). Y
G804D missense unknown ERBB2 (HER2) G804D lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). G804D has not been characterized in the scientific literature and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
G804S missense unknown ERBB2 (HER2) G804S lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). G804S has not been characterized, but is predicted to activate the kinase activity of Erbb2 (Her2) by structural modeling (PMID: 24817905).
G919W missense unknown ERBB2 (HER2) G919W lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). G919W demonstrates decreased transformation ability as compared to wild-type Erbb2 (Her2) in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
H473N missense no effect - predicted ERBB2 (HER2) H473N lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). H473N has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
H878Y missense gain of function ERBB2 (HER2) H878Y lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). H878Y confers a gain of function to the Erbb2 (Her2) protein as demonstrated by increased Erbb2 (Her2) phosphorylation and transformation of cells in cell culture (PMID: 22046346).
I101S missense no effect - predicted ERBB2 (HER2) I101S lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). I101S has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
I654V missense unknown ERBB2 (HER2) I654V lies within the transmembrane domain of the Erbb2 (Her2) protein (UniProt.org). I654V has not been biochemically characterized, however, computational analysis indicates it is predicted to stabilize Erbb2 (Her2) dimerization, resulting in increased autophosphorylation and protein kinase activity (PMID: 15550452), and therefore, its effect on Erbb2 (Her2) protein function is unknown.
I655V missense no effect - predicted ERBB2 (HER2) I655V is a common Erbb2 (Her2) polymorphism (PMID: 21474413, PMID: 14578152) that lies within the transmembrane domain of the Erbb2 (Her2) protein (PMID: 18178548). I655V results in similar cell proliferation and viability levels to wild-type Erbb2 (Her2) in two different cell lines (PMID: 29533785), and similar structural morphology to wild-type Erbb2 in culture (PMID: 27697991), and therefore, is predicted to have no effect on Erbb2 (Her2) protein function.
I767M missense unknown ERBB2 (HER2) I767M lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). I767M results in increased Erbb2 (Her2) kinase activity, sustained Akt phosphorylation, and is transforming in cell culture (PMID: 25994018, PMID: 29967253), however, in another study I767M results in similar cell proliferation and viability levels to wild-type Erbb2 (Her2) in two different cell lines in culture (PMID: 29533785), and therefore, its effect on Erbb2 (Her2) protein function is unknown.
K228N missense no effect - predicted ERBB2 (HER2) K228N lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). K228N has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
K676R missense no effect ERBB2 (HER2) K676R lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). K676R confers no effect to the Erbb2 (Her2) protein, resulting in kinase activity, phosphorylation, and cell morphology in culture similar to wild-type (PMID: 27697991).
K716E missense unknown ERBB2 (HER2) K716E lies within the cytoplasmic domain of the Erbb2 (Her2) protein (UniProt.org). K716E demonstrates decreased transformation ability compared to wild-type Erbb2 (Her2) in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
K716Q missense unknown ERBB2 (HER2) K716Q lies within the cytoplasmic domain of the Erbb2 (Her2) protein (UniProt.org). K716Q has not been characterized in the scientific literature and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
K753A missense loss of function - predicted ERBB2 (HER2) K753A lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). K753A has been described as a kinase deficient mutation and is predicted to confer a loss of function to the Erbb2 (Her2) protein as demonstrated by loss of protein kinase activity (PMID: 22393464).
K753E missense unknown ERBB2 (HER2) K753E lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). K753E does not result in increased phosphorylation of Erbb2 (Her2) or downstream PLC-gamma, and results in similar tumor formation to wild-type Erbb2 (Her2) in mouse models, however, results in increased Egfr phosphorylation and is associated with resistance to some Erbb2 (Her2) inhibitors (PMID: 27697991, PMID: 29389942). Y
K753M missense loss of function - predicted ERBB2 (HER2) K753M lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). K753M has been described as a kinase dead mutation and is predicted to confer a loss of function to the Erbb2 (Her2) protein as demonstrated by loss of Erbb2 (Her2) phosphorylation (PMID: 16489002).
K831N missense unknown ERBB2 (HER2) K831N lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). K831N has been identified in the scientific literature (PMID: 29420467), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
K937R missense unknown ERBB2 (HER2) K937R lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). K937R demonstrates decreased transformation ability as compared to wild-type Erbb2 (Her2) in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
L145F missense no effect - predicted ERBB2 (HER2) L145F lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). L145F has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
L313I missense unknown ERBB2 (HER2) L313I lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). L313I has been identified in the scientific literature (PMID: 30301790, PMID: 25975284), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Sep 2019).
L313V missense unknown ERBB2 (HER2) L313V lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). L313V demonstrates decreased transformation ability as compared to wild-type Erbb2 (Her2) in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019)
L49H missense no effect ERBB2 (HER2) L49H lies within the extracellular domain of the Erbb2 (Her2) protein (PMID: 22908275). L49H demonstrates phosphorylation level and transformation potential comparable to wild-type Erbb2 (Her2) protein in cell culture (PMID: 22908275).
L663P missense unknown ERBB2 (HER2) L663P lies within the transmembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). L663P is conflicting as it results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) in one study (PMID: 29533785), but in another study when expressed in cells in the presence of wild-type Erbb2 (Her2), it results in large multi-acinar bodies and increased cell survival as compared to wild-type in culture (PMID: 30449325), and therefore, its effect on Erbb2 (Her2) protein function is unknown.
L720V missense unknown ERBB2 (HER2) L720V lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). L720V has not been characterized in the scientific literature and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
L726F missense gain of function ERBB2 (HER2) L726F lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). L726F confers a gain of function to the Erbb2 (Her2) protein as indicated by increased cell proliferation in culture, increased tumor growth in vivo, and localization to the perinuclear cytoplasm (PMID: 25435280).
L726I missense unknown ERBB2 (HER2) L726I lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). L726I is associated with resistance to Iressa (gefitinib) and Tykerb (lapatinib) in cell culture (PMID: 17638894, PMID: 18413839), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019). Y
L755A missense unknown ERBB2 (HER2) L755A lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). L755A has been identified in the scientific literature (PMID: 28167203, PMID: 29989854), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
L755M missense no effect - predicted ERBB2 (HER2) L755M lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). L755M has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
L755P missense gain of function ERBB2 (HER2) L755P lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). L755P results in increased phosphorylation of Erbb2 (Her2), activation of downstream signaling, is transforming in cell culture (PMID: 22046346, PMID: 29967253, PMID: 31588020), and confers resistance to selected tyrosine kinase inhibitors (PMID: 31588020). Y
L755S missense gain of function ERBB2 (HER2) L755S lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). L755S results in increased phosphorylation of Erbb2 (Her2), activation of downstream signaling, is transforming in cell culture (PMID: 29967253, PMID: 31588020), and is associated with resistance to Erbb2 (Her2)-targeted therapies (PMID: 22046346, PMID: 28487443). Y
L755W missense unknown ERBB2 (HER2) L755W lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). L755W has been identified in the scientific literature (PMID: 23220880, PMID: 27811364), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
L755X missense unknown ERBB2 (HER2) L755X indicates any ERBB2 (HER2) missense mutation that results in the leucine (L) at amino acid 755 being replaced by a different amino acid.
L755_E757del deletion unknown ERBB2 (HER2) L755_E757del results in the deletion of three amino acids in the protein kinase domain of the Erbb2 (Her2) protein from amino acids 755 to 757 (UniProt.org). L755_E757del has not been characterized in the scientific literature and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
L755_E757delinsS insertion unknown ERBB2 (HER2) L755_E757delinsS results in the deletion of three amino acids from aa 755 to 757 within the protein kinase domain of the Erbb2 (Her2) protein, combined with the insertion of a serine (S) at the same site (UniProt.org). L755_E757delinsS has been identified in the scientific literature (PMID: 29420467), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
L755_T759del deletion gain of function ERBB2 (HER2) L755_T759del results in the deletion of five amino acids in the protein kinase domain of the Erbb2 (Her2) protein from amino acids 755 to 759 (UniProt.org). L755_T759del confers a gain of function to the Erbb2 (Her2) protein as demonstrated by increased phosphorylation of Egfr and Erbb3 (Her3), tumor growth (PMID: 23220880), and is transforming in cell culture (PMID: 29533785).
L768S missense gain of function ERBB2 (HER2) L768S lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). L768S confers a gain of function to the Erbb2 (Her2) protein as demonstrated by increased tyrosine kinase activity and phosphorylation compared to wild-type, and abnormal cellular morphology in culture (PMID: 27697991).
L785F missense unknown ERBB2 (HER2) L785F lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). L785F confers Tykerb (lapatinib)-resistance in cell culture (PMID: 18413839), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019). Y
L786V missense gain of function ERBB2 (HER2) L786V lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). L786V results in constitutive phosphorylation of Erbb2 (Her2), increased downstream signaling, is transforming in cell culture, and confers resistance to selected tyrosine kinase inhibitors (PMID: 31588020). Y
L841V missense gain of function - predicted ERBB2 (HER2) L841V lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). L841V has not been biochemically characterized, but in two different cell lines, L841V induced increased cell proliferation and cell viability as compared to wild-type Erbb2 (Her2) (PMID: 29533785) and demonstrated transformation in cell culture (PMID: 29967253) and therefore, is predicted to result in a gain of Erbb2 (Her2) protein function.
L866M missense gain of function ERBB2 (HER2) L866M lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). L866M results in constitutive phosphorylation of Erbb2 (Her2) and increased phosphorylation of Mapk in cell culture (PMID: 26243863).
L869Q missense unknown ERBB2 (HER2) L869Q lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). L869Q has been identified in the scientific literature (PMID: 26487584, PMID: 27602491, PMID: 28274957), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
L869R missense gain of function ERBB2 (HER2) L869R lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). L869R results in constitutive Erbb2 (Her2) phosphorylation, activation of downstream signaling, transformation of cultured cells (PMID: 31588020), enhanced tumor formation and metastasis in animal models (PMID: 27900369), and confers resistance to selected tyrosine kinase inhibitors (PMID: 31588020). Y
L915M missense unknown ERBB2 (HER2) L915M lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). L915M confers Tykerb (lapatinib)-resistance in cell culture (PMID: 18413839), but has not been biochemically characterized and therefore its effect on Erbb2 (Her2) protein is unknown (PubMed, Oct 2019). Y
M774delinsWLV indel gain of function ERBB2 (HER2) M774delinsWLV results in a deletion of methionine (M) at amino acid 774 within the protein kinase domain of the Erbb2 (Her2) protein, combined with the insertion of a tryptophan (W), lysine (L), and a valine (V) at the same site (UniProt.org). M774delinsWLV results in activation of Erbb2 (Her2) and transformation of cultured cells (PMID: 28363995).
M774_A775insAYVM insertion gain of function ERBB2 (HER2) M774_A775insAYVM results in the insertion of four amino acids in the protein kinase domain of the Erbb2 (Her2) protein between amino acids 774 and 775 (UniProt.org). M774_A775insAYVM results in constitutive phosphorylation of Erbb2 (Her2) and is transforming in cell culture (PMID: 17311002).
M916I missense unknown ERBB2 (HER2) M916I lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). M916I demonstrates decreased transformation ability as compared to wild-type Erbb2 (Her2) in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
M953I missense no effect - predicted ERBB2 (HER2) M953I lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). M953I has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
mutant unknown unknown ERBB2 (HER2) mutant indicates an unspecified mutation in the ERBB2 (HER2) gene.
N1219S missense no effect - predicted ERBB2 (HER2) N1219S lies within the cytoplasmic domain of the Erbb2 (Her2) protein (UniProt.org). N1219S has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
N319D missense no effect ERBB2 (HER2) N319D lies within the extracellular domain of the Erbb2 (Her2) protein (PMID: 22908275). N319D demonstrates phosphorylation level and transformation potential comparable to wild-type Erbb2 (Her2) protein in cell culture (PMID: 22908275).
N571K missense no effect - predicted ERBB2 (HER2) N571K lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). N571K has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
N813D missense unknown ERBB2 (HER2) N813D lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). N813D has been identified in the scientific literature (PMID: 29215816), but has not been biochemically characterized, and therefore its effect on Erbb2 (Her2) protein function is unknown (PubMed, Sep 2019).
N857S missense gain of function ERBB2 (HER2) N857S lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). N857S results in constitutive phosphorylation of Erbb2 (Her2) and is transforming in cell culture (PMID: 22046346).
negative unknown loss of function ERBB2 (HER2) negative indicates a lack of the ERBB2 (HER2) gene, mRNA, and/or protein.
over exp none no effect ERBB2 (HER2) over exp indicates an over expression of the Erbb2 (Her2) protein and/or mRNA. However, the mechanism causing the over expression is unknown.
P1074L missense unknown ERBB2 (HER2) P1074L lies within the cytoplasmic domain of the Erbb2 (Her2) protein (PMID: 30531871). P1074L has been identified in the scientific literature (PMID: 30531871), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Sep 2019).
P1170A missense no effect - predicted ERBB2 (HER2) P1170A lies within the cytoplasmic domain of the Erbb2 (Her2) protein (UniProt.org). P1170A is a common polymorphism (PMID: 15743501) that has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
P1207A missense unknown ERBB2 (HER2) P1207A lies within the cytoplasmic domain of the Erbb2 (Her2) protein (UniProt.org). P1207A has been identified in sequencing studies (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
P1210S missense no effect - predicted ERBB2 (HER2) P1210S lies within the cytoplasmic domain of the Erbb2 (Her2) protein (UniProt.org). P1210S has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
P122Q missense no effect - predicted ERBB2 (HER2) P122Q lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). P122Q has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
P1234S missense no effect - predicted ERBB2 (HER2) P1234S lies within the cytoplasmic domain of the Erbb2 (Her2) protein (UniProt.org). P1234S has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
P197S missense unknown ERBB2 (HER2) P197S lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). P197S has been identified in sequencing studies (PMID: 25589618), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
P230L missense unknown ERBB2 (HER2) P230L lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). P230L has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
P247S missense no effect - predicted ERBB2 (HER2) P247S lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). P247S has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
P36S missense no effect - predicted ERBB2 (HER2) P36S lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). P36S has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
P391Q missense no effect - predicted ERBB2 (HER2) P391Q lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). P391Q has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
P416L missense no effect - predicted ERBB2 (HER2) P416L lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). P416L has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
P489L missense no effect - predicted ERBB2 (HER2) P489L lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). P489L has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
P489Q missense unknown ERBB2 (HER2) P489Q lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). P489Q demonstrates decreased transformation ability as compared to wild-type Erbb2 (Her2) in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
P551L missense unknown ERBB2 (HER2) P551L lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). P551L demonstrates increased transformation ability as compared to wild-type Erbb2 (Her2) in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
P702L missense unknown ERBB2 (HER2) P702L lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). P702L has been identified in the scientific literature (PMID: 31685261, PMID: 30449325), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Dec 2019).
P761del deletion unknown ERBB2 (HER2) P761del results in the deletion of one amino acid in the protein kinase domain of the Erbb2 (Her2) protein at amino acid 761 (UniProt.org). P761del has been identified in the scientific literature (PMID: 29420467), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
P780L missense unknown ERBB2 (HER2) P780L lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). P780L confers resistance to Tykerb (lapatinib) in cell culture (PMID: 18413839), but has not been biochemically characterized and therefore its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019). Y
P780_Y781insGSP insertion gain of function ERBB2 (HER2) P780_Y781insGSP (also referred to as G778_P780dup) results in the insertion of three amino acids in the protein kinase domain of the Erbb2 (Her2) protein between amino acids 780 and 781 (UniProt.org). P780_Y781insGSP results in constitutive activation of Erbb2 (Her2), increased downstream signaling, and is transforming in cell culture (PMID: 23220880, PMID: 28363995, PMID: 29967253).
P885S missense unknown ERBB2 (HER2) P885S lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). P885S demonstrates decreased transformation ability as compared to wild-type Erbb2 (Her2) in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
positive unknown unknown ERBB2 (HER2) positive indicates the presence of the ERBB2 (HER2) gene, mRNA, and/or protein. ERBB2 (HER2) positive has been used alternatively to refer to overexpression and/or amplification of ERBB2 (HER2). For related data, refer to ERBB2 amp or ERBB2 overexp in CKB.
Q679L missense gain of function ERBB2 (HER2) Q679L lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). Q679L confers a gain of function to the Erbb2 (Her2) protein as indicated by increased phosphorylation of Erbb2 (Her2), downstream signaling, and colony formation, and is transforming in cell culture (PMID: 31046123).
Q680R missense no effect ERBB2 (HER2) Q680R lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). Q680R confers no effect to the Erbb2 (Her2) protein, resulting in kinase activity, phosphorylation, and cell morphology in culture similar to wild-type (PMID: 27697991).
Q709L missense gain of function ERBB2 (HER2) Q709L lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). Q709L results in increased cell survival in the presence of wild-type Erbb2 (Her2) and demonstrates elevated Erbb2 (Her2) phosphorylation compared to wild-type Erbb2 (Her2) in vitro and the formation of large multi-acinar bodies in culture, both in the presence and absence of wild-type Erbb2 (Her2) (PMID: 30449325).
Q711H missense no effect - predicted ERBB2 (HER2) Q711H lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). Q711H has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
Q943* nonsense unknown ERBB2 (HER2) Q943* results in a premature truncation of the Erbb2 (Her2) protein at amino acid 943 of 1255 (UniProt.org). Q943* has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
R1006C missense no effect - predicted ERBB2 (HER2) R1006C lies within the cytoplasmic domain of the Erbb2 (Her2) protein (UniProt.org). R1006C has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
R1053M missense no effect - predicted ERBB2 (HER2) R1053M lies within the cytoplasmic domain of the Erbb2 (Her2) protein (UniProt.org). R1053M has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
R1153* nonsense unknown ERBB2 (HER2) R1153* results in a premature truncation of the Erbb2 (Her2) protein at amino acid 1229 of 1255 (UniProt.org). R1153* has been identified in the scientific literature (PMID: 29420467, PMID: 23575477), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
R1153L missense unknown ERBB2 (HER2) R1153L lies within the cytoplasmic domain of the Erbb2 (Her2) protein (PMID: 30531871). R1153L has been identified in the scientific literature (PMID: 30531871), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Sep 2019).
R138W missense no effect - predicted ERBB2 (HER2) R138W lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). R138W has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
R143G missense unknown ERBB2 (HER2) R143G lies within the extracellular domain of the Erbb2 (Her2) protein (PMID: 30531871). R143G has been identified in the scientific literature (PMID: 30531871), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Sep 2019).
R217C missense unknown ERBB2 (HER2) R217C lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). R217C has not been characterized in the scientific literature and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
R217H missense unknown ERBB2 (HER2) R217H lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). R217H has been identified in sequencing studies (PMID: 30348637, PMID: 29718453), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Feb 2020).
R226S missense unknown ERBB2 (HER2) R226S lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). R226S demonstrates increased transformation ability as compared to wild-type Erbb2 (Her2) in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
R432W missense unknown ERBB2 (HER2) R432W lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). R432W has been identified in sequencing studies (PMID: 27363283), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
R456C missense unknown ERBB2 (HER2) R456C lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). R456C has been identified in the scientific literature (PMID: 30301790), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Sep 2019).
R487W missense no effect - predicted ERBB2 (HER2) R487W lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). R487W has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
R545* nonsense loss of function - predicted ERBB2 (HER2) R545* results in a premature truncation of the Erbb2 (Her2) protein at amino acid 545 of 1255 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), R545* is predicted to lead to a loss of Erbb2 (Her2) protein function.
R647K missense no effect ERBB2 (HER2) R647K lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). R647K confers no effect to the Erbb2 (Her2) protein, resulting in kinase activity, phosphorylation, and cell morphology in culture similar to wild-type (PMID: 27697991).
R677L missense gain of function - predicted ERBB2 (HER2) R677L lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). R677L results in increased cell survival as compared wild-type Erbb2 (Her2) in culture (PMID: 30449325), and therefore, is predicted to result in a gain of Erbb2 (Her2) protein function.
R678L missense unknown ERBB2 (HER2) R678L lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). R678L has been identified in the scientific literature (PMID: 25636205), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
R678Q missense unknown ERBB2 (HER2) R678Q lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). The functional effect of R678Q is conflicting, as it demonstrates phosphorylation levels and transformation potential comparable to wild-type Erbb2 (Her2) protein in cell culture and xenograft models (PMID: 29533785, PMID: 23220880), however, in other studies, results in increased phosphorylation of Erbb2 (Her2) and activation of downstream signaling, and is transforming in culture (PMID: 30449325, PMID: 31588020). Y
R678W missense gain of function - predicted ERBB2 (HER2) R678W lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). R678W results in increased cell survival as compared to wild-type Erbb2 (Her2) in culture (PMID: 30449325) and therefore, is predicted to result in a gain of Erbb2 (Her2) protein function.
R683Q missense no effect - predicted ERBB2 (HER2) R683Q lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). R683Q has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
R784G missense unknown ERBB2 (HER2) R784G lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). R784G has been associated with resistance to Egfr antibodies (PMID: 30549033), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Sep 2019). Y
R784H missense unknown ERBB2 (HER2) R784H lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). R784H has been identified in the scientific literature (PMID: 24797764), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
R868W missense loss of function ERBB2 (HER2) R868W lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). R868W results in decreased Erbb2 (Her2) and Mapk phosphorylation in cell culture (PMID: 28743916), and in one of two cell lines, R868W decreased cell proliferation and cell viability as compared to wild-type Erbb2 (Her2) (PMID: 29533785).
R896C missense gain of function ERBB2 (HER2) R896C lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). R896C results in constitutive phosphorylation of Erbb2 (Her2), increased downstream signaling, and is transforming in cell culture (PMID: 23220880).
R897Q missense no effect - predicted ERBB2 (HER2) R897Q lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). R897Q has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, is predicted to have no effect on Erbb2 (Her2) protein function.
R966C missense loss of function ERBB2 (HER2) R966C lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). R966C results in decreased Erbb2 (Her2) and Mapk phosphorylation in cell culture (PMID: 28743916).
R970W missense unknown ERBB2 (HER2) R970W lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). R970W has been identified in the scientific literature (PMID: 21347793), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
S1002R missense unknown ERBB2 (HER2) S1002R lies within the cytoplasmic domain of the Erbb2 (Her2) protein (UniProt.org). S1002R confers Tykerb (lapatinib)-resistance in cell culture (PMID: 18413839), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019). Y
S250F missense unknown ERBB2 (HER2) S250F lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). S250F has been identified in sequencing studies (PMID: 29420467, PMID: 29522538), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
S305F missense no effect - predicted ERBB2 (HER2) S305F lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). S305F has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
S310F missense gain of function ERBB2 (HER2) S310F lies within the extracellular domain of the Erbb2 (Her2) protein (PMID: 22908275). S310F confers a gain of function to Erbb2 (Her2) as indicated by increased phosphorylation of Erbb2 (Her2) and downstream signaling, colony formation, migration, transformation in cell culture (PMID: 22908275, PMID: 29533785, PMID: 29967253, PMID: 29954840), and enhanced tumor growth in mouse models (PMID: 29954840).
S310Y missense gain of function ERBB2 (HER2) S310Y lies within the extracellular domain of the Erbb2 (Her2) protein (PMID: 22908275). S310Y confers a gain of function to Erbb2 (Her2) as indicated by increased downstream p-AKT and p-ERK signaling, colony formation, migration, and transformation potential in cell culture (PMID: 22908275, PMID: 29967253; PMID: 29954840), increased cell proliferation and cell viability as compared to wild-type Erbb2 (Her2) in one of two cell lines (PMID: 29533785), and enhanced tumor growth in mouse models (PMID: 29954840).
S423R missense gain of function ERBB2 (HER2) S423R lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). S423R confers a gain of function to the Erbb2 (Her2) protein as indicated by increased phosphorylation of Erbb2 (Her2), downstream signaling, and colony formation, and is transforming in cell culture (PMID: 31046123).
S573L missense no effect - predicted ERBB2 (HER2) S573L lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). S573L has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
S653C missense gain of function ERBB2 (HER2) S653C lies within the transmembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). S653C results in constitutive activation of Erbb2 (Her2) and phosphorylation of Shc and Erk in cell culture (PMID: 24971884) and leads to increased cell survival as compared to wild-type Erbb2 (Her2) in culture (PMID: 30449325).
S656C missense gain of function - predicted ERBB2 (HER2) S656C lies within the transmembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). S656C results in increased cell survival as compared to wild-type Erbb2 (Her2) in cell culture (PMID: 30449325), and therefore, is predicted to result in a gain of Erbb2 (Her2) protein function.
S760A missense no effect ERBB2 (HER2) S760A lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). S760A did not demonstrate an independent functional effect, however, has been shown to occur with other Erbb2 (Her2) activating mutations, including L755_T759del (PMID: 23220880).
S779_P780insVGS insertion gain of function - predicted ERBB2 (HER2) S779_P780insVGS results in the insertion of three amino acids in the protein kinase domain of the Erbb2 (Her2) protein between amino acids 779 and 780 (UniProt.org). S779_P780insVGS has not been characterized, however other exon 20 insertions are activating thus, S779_P780insVGS is predicted to lead to gain of Erbb2 (Her2) function (PMID: 16843263, PMID: 17311002, PMID: 23220880).
S783P missense no effect - predicted ERBB2 (HER2) S783P lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). S783P is predicted to have no effect on Erbb2 (Her2) protein function, as it does not result in increased phosphorylation of Erbb2 (Her2) or downstream targets in cultured cells (PMID: 28164408), however, is associated with Tykerb (lapatinib)-resistance in cell culture (PMID: 18413839). Y
S974A missense unknown ERBB2 (HER2) S974A lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). S974A has not been characterized in the scientific literature and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
S974F missense unknown ERBB2 (HER2) S974F lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org).S974F demonstrates decreased transformation ability as compared to wild-type Erbb2 (Her2) in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
T182I missense no effect - predicted ERBB2 (HER2) T182I lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). T182I has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, is predicted to have no effect on Erbb2 (Her2) protein function.
T216S missense gain of function - predicted ERBB2 (HER2) T216S lies within the extracellular domain of the Erbb2 (Her2) protein (PMID: 22908275). T216S is predicted to confer a gain of function to the Erbb2 (Her2) protein as demonstrated by increased kinase activity (PMID: 22908275).
T306M missense no effect - predicted ERBB2 (HER2) T306M lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). T306M has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
T496I missense unknown ERBB2 (HER2) T496I lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). T496I has not been characterized in the scientific literature and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
T652R missense no effect - predicted ERBB2 (HER2) T652R lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). T652R has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
T686A missense gain of function - predicted ERBB2 (HER2) T686A lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). T686A results in increased cell survival as compared to wild-type Erbb2 (Her2) in culture (PMID: 30449325) and therefore, is predicted to result in a gain of Erbb2 (Her2) protein function.
T686M missense no effect - predicted ERBB2 (HER2) T686M lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). T686M has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
T733I missense no effect - predicted ERBB2 (HER2) T733I lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). T733I has not been biochemically characterized, but has weak transformation activity (PMID: 18413839) and induces similar cell proliferation and cell viability as wild-type Erbb2 (Her2), in two different cell lines (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
T798I missense no effect - predicted ERBB2 (HER2) T798I lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). T798I does not result in activation of Erbb2 (Her2) downstream signaling or transformation of cultured cells, but is associated with resistance to Erbb2 (Her2) inhibitors (PMID: 25238247, PMID: PMID: 28274957, PMID: 18413839) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function. Y
T798M missense gain of function ERBB2 (HER2) T798M lies within the gatekeeper position in the ATP binding site of the Erbb2 (Her2) protein. T798M results in activation of the Erbb2 (Her2) protein in cell culture experiments (PMID: 22046346, PMID: 23948973) and demonstrates the ability to increase cell proliferation and cell viability in culture (PMID: 29533785).
T862A missense gain of function ERBB2 (HER2) T862A lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). T862A results in constitutive phosphorylation of Erbb2 (Her2) and is transforming in cell culture (PMID: 22046346, PMID: 29533785, PMID: 29967253).
T862I missense unknown ERBB2 (HER2) T862I lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). T862I has been identified in sequencing studies (PMID: 24983367), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Feb 2020).
V308M missense unknown ERBB2 (HER2) V308M lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). V308M results in decreased cell proliferation and cell viability compared to wild-type Erbb2 (Her2) in one of two cell lines in culture (PMID: 29533785), however, has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
V659E missense gain of function ERBB2 (HER2) V659E lies within the transmembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). V659E results in constitutive phosphorylation of Erbb2 (Her2), activation of Src and Akt signaling in cell culture, and increased tumor metastasis in animal models (PMID: 16489002, PMID: 15753384), and leads to increased cell survival as compared to wild-type Erbb2 (Her2) in culture (PMID: 30449325), and in one of two cell lines, V659E increased cell proliferation and cell viability as compared to wild-type Erbb2 (Her2) (PMID: 29533785).
V697L missense unknown ERBB2 (HER2) V697L lies within the juxtamembrane domain of the Erbb2 (Her2) protein (PMID: 30449325). V697L has been identified in the scientific literature (PMID: 29247016, PMID: 28679771), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
V750E missense loss of function - predicted ERBB2 (HER2) V750E lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). V750E is predicted to confer a loss of function to the Erbb2 (Her2) protein as demonstrated by decreased kinase activity (PMID: 22908275).
V754M missense gain of function ERBB2 (HER2) V754M lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). V754M results in increased Erbb2 (Her2) phosphorylation and activation of downstream signaling, and is transforming in cell culutre (PMID: 31588020).
V773A missense gain of function ERBB2 (HER2) V773A lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). V773A results in constitutive phosphorylation of Erbb2 (Her2) and is transforming in cell culture (PMID: 22046346).
V773L missense gain of function ERBB2 (HER2) V773L lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). V773L confers a gain of function to the Erbb2 (Her2) protein as demonstrated by increased tyrosine kinase activity and phosphorylation compared to wild-type, and abnormal cellular morphology in culture (PMID: 27697991).
V773M missense unknown ERBB2 (HER2) V773M lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). V773M results in activation of Erbb2 downstream signaling, is transforming in cell culture, and confers resistance to selected tyrosine kinase inhibitors (PMID: 31588020), but also demonstrates similar levels of cell proliferation and viability as wild-type Erbb2 (Her2) (PMID: 29533785), and therefore, its effect on Erbb2 (Her2) protein function is unknown. Y
V777A missense loss of function ERBB2 (HER2) V777A lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). V777A results in decreased Erbb2 (Her2) activity and a decreased ability to transform cells in culture (PMID: 22908275).
V777L missense gain of function ERBB2 (HER2) V777L lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). V777L results in increased Erbb2 (Her2) activity, activation of downstream signaling, transformation of cultured cells (PMID: 29967253, PMID: 31588020), increased tumor growth in xenograft models (PMID: 23220880), and confers resistance to selected tyrosine kinase inhibitors (PMID: 31588020). Y
V777M missense unknown ERBB2 (HER2) V777M lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). V777M has been identified in the scientific literature (PMID: 22761469, PMID: 28481359, PMID: 27284958), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
V777_G778insG insertion gain of function - predicted ERBB2 (HER2) V777_G778insG results in the insertion of a glycine (G) in the protein kinase domain of the Erbb2 (Her2) protein between amino acids 777 and 778 (UniProt.org). V777_G778insG has not been characterized, however other exon 20 insertions are activating thus, G778_S779insG is predicted to lead to gain of Erbb2 (Her2) function (PMID: 16843263, PMID: 17311002, PMID: 23220880).
V782I missense no effect - predicted ERBB2 (HER2) V782I lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). V782I has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
V839G missense unknown ERBB2 (HER2) V839G lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). V839G confers Tykerb (lapatinib)-resistance in cell culture (PMID: 18413839), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019). Y
V842E missense unknown ERBB2 (HER2) V842E lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). V842E demonstrates decreased transformation ability as compared to wild-type Erbb2 (Her2) in one of two different cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019).
V842I missense unknown ERBB2 (HER2) V842I lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). V842I confers resistance to selected tyrosine kinase inhibitors (PMID: 31588020), results in increased Erbb2 (Her2) activity, downstream pathway activation, and transformation of cultured cells (PMID: 23220880, PMID: 31588020), however, in another study, demonstrates similar cell proliferation and viability levels to wild-type Erbb2 (Her2) in two different cell lines (PMID: 29533785), and therefore, its effect on Erbb2 (Her2) protein function is unknown. Y
W825* nonsense loss of function - predicted ERBB2 (HER2) W825* results in a premature truncation within the protein kinase domain of the Erbb2 (Her2) protein at amino acid 825 of 1255 (UniProt.org). Due to the disruption of the protein kinase domain (UniProt.org), W825* is predicted to lead to a loss of Erbb2 (Her2) protein function.
W906* nonsense loss of function - predicted ERBB2 (HER2) W906* results in a premature truncation of the Erbb2 (Her2) protein within the protein kinase domain of the Erbb2 (Her2) protein at amino acid 906 of 1255 (UniProt.org). Due to the disruption of the Erbb2 (Her2) kinase domain, W906* is predicted to lead to a loss of function.
wild-type none no effect Wild-type ERBB2 (HER2) indicates that no mutation has been detected within the ERBB2 (HER2) gene.
Y1248F missense loss of function - predicted ERBB2 (HER2) Y1248F lies within the cytoplasmic domain of the Erbb2 (Her2) protein (UniProt.org). Y1248F results in constitutive dephosphorylation of Erbb2 (Her2), which leads to endosomal internalization and lysosomal degradation of Erbb2 (Her2) in cell lines (PMID: 27345410) and therefore, is predicted to result in a loss of Erbb2 (Her2) protein function.
Y772_A775dup duplication gain of function ERBB2 (HER2) Y772_A775dup (also referred to as A775_G776insYVMA, M774_A775insAYVM, and E770delinsEAYVM) indicates the insertion of 4 duplicate amino acids, tyrosine (Y)-772 through alanine (A)-775, in the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). Y772_A775dup results in the constitutive phosphorylation of Erbb2 (Her2), activation of downstream signaling, is transforming in cell culture (PMID: 17311002, PMID: 31588020), and confers resistance to selected tyrosine kinase inhibitors (PMID: 31588020). Y
Y803H missense no effect - predicted ERBB2 (HER2) Y803H lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). Y803H has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Erbb2 (Her2) (PMID: 29533785) and therefore, it is predicted to have no effect on Erbb2 (Her2) protein function.
Y803N missense unknown ERBB2 (HER2) Y803N lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). Y803N is associated with Tykerb (lapatinib)-resistance in cell culture (PMID: 18413839), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Oct 2019). Y
Y835F missense unknown ERBB2 (HER2) Y835F lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). Y835F results in decreased Erbb2 (Her2) kinase activity, reduced cell proliferation, and is not transforming in culture in one study (PMID: 23220880), and in another study, results in similar cell proliferation and viability levels to wild-type Erbb2 (Her2) in two different cell lines (PMID: 29533785), and therefore its effect on Erbb2 (Her2) protein function is unknown.