Gene Variant Detail

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Gene ERBB2
Variant A775_G776insYVMA
Impact List insertion
Protein Effect gain of function
Gene Variant Descriptions 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).
Associated Drug Resistance

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Transcript NM_004448
gDNA chr17:g.39724743_39724744insTATGTAATGGCA
cDNA c.2325_2326insTATGTAATGGCA
Protein p.Y772_A775dupYVMA
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_001289937 chr17:g.39724743_39724744insTATGTAATGGCA c.2325_2326insTATGTAATGGCA p.Y772_A775dupYVMA RefSeq GRCh38/hg38
NM_004448 chr17:g.39724743_39724744insTATGTAATGGCA c.2325_2326insTATGTAATGGCA p.Y772_A775dupYVMA RefSeq GRCh38/hg38

Filtering

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  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
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  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Protein Effect Treatment Approaches
ERBB2 A775_G776insYVMA gain of function HER inhibitor (Pan) HER2 Inhibitor
ERBB2 A775_G776insYVMA PIK3CA R425L
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ERBB2 A775_G776insYVMA lung non-small cell carcinoma sensitive Ado-trastuzumab emtansine Preclinical - Pdx Actionable In a preclinical study, treatment with Kadcyla (ado-trastuzumab emtansine) resulted in tumor growth inhibition and tumor regression of patient derived xenograft (PDX) models harboring ERBB2 A775_G776insYVMA, but to a lesser degree than treatment with Pyrotinib (PMID: 30596880; NCT02535507). 30596880
ERBB2 A775_G776insYVMA lung non-small cell carcinoma sensitive Afatinib Preclinical - Pdx & cell culture Actionable In a preclinical study, treatment with Gilotrif (afatinib) resulted in decreased cell viability of patient-derived non-small cell lung cancer organoids harboring ERBB2 A775_G776insYVMA and tumor growth inhibition and tumor regression in patient derived xenograft (PDX) models, but to a lesser degree than treatment with Pyrotinib (PMID: 30596880; NCT02535507). 30596880
ERBB2 A775_G776insYVMA lung adenocarcinoma predicted - sensitive Ado-trastuzumab emtansine Case Reports/Case Series Actionable In a Phase II trial, treatment with Kadcyla (trastuzumab emtansine) resulted in best overall responses of partial response in 44% (8/18) and stable disease in 39% (7/18), and median progression-free survival of 5 months in patients with lung adenocarcinoma harboring ERBB2 (HER2) activating mutations, and a subset of patients specifically harboring ERBB2 (HER2) A775_G776insYVMA mutation had a 60% (3/5) partial response rate (PMID: 29989854; NCT02675829). 29989854
ERBB2 A775_G776insYVMA Advanced Solid Tumor sensitive JQ1 + Osimertinib Preclinical Actionable In a preclinical study, transgenic mouse models expressing ERBB2 (HER2) A775_G776insYVMA demonstrated greater tumor regression when treated with the combination of JQ1 and Tagrisso (osimertinib) compared to treatment with either agent alone, which resulted in little to no regression (PMID: 29298799). 29298799
ERBB2 A775_G776insYVMA lung non-small cell carcinoma sensitive Pyrotinib Case Reports/Case Series Actionable In a Phase II trial, ten patients with non-small cell lung cancer harboring ERBB2 A775_G776insYVMA demonstrated an objective response rate of 50% (5/10) and a progression-free survival of 4.1 months when treated with Pyrotinib, and preclinical analysis showed Pyrotinib treatment led to reduced cell viability in patient-derived organoids and tumor growth inhibition and regression in patient derived xenograft (PDX) models (PMID: 30596880; NCT02535507). 30596880
ERBB2 A775_G776insYVMA PIK3CA R425L lung non-small cell carcinoma predicted - resistant Trastuzumab Case Reports/Case Series Actionable In a clinical study, the PIK3CA R425L mutation was identified as a potential resistance mechanism in a non-small cell lung carcinoma patient harboring ERBB2 (HER2) A775_G776insYVMA, that progressed during Herceptin (trastuzumab) treatment (PMID: 28167203). 28167203