Gene Variant Detail

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Gene ERBB2
Variant Y772_A775dup
Impact List duplication
Protein Effect gain of function
Gene Variant Descriptions 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).
Associated Drug Resistance Y

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Transcript NM_004448
gDNA chr17:g.39724732_39724743
cDNA c.2314_2325
Protein p.Y772_A775
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_001289937 chr17:g.39724732_39724743 c.2314_2325 p.Y772_A775 RefSeq GRCh38/hg38
NM_004448 chr17:g.39724732_39724743 c.2314_2325 p.Y772_A775 RefSeq GRCh38/hg38

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  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • 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 )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ERBB2 Y772_A775dup Advanced Solid Tumor resistant Nazartinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup were resistant to Nazartinib (EGF816) in culture (PMID: 31588020). 31588020
ERBB2 Y772_A775dup lung cancer sensitive Afatinib Preclinical Actionable In a preclinical study, Gilotrif (afatinib) inhibited Erbb2 (Her2) phosphorylation and downstream signaling in bronchial epithelial cells expressing ERBB2 (HER2) Y772_A775dup (also referred to as A775_G776insYVMA) in culture (PMID: 26545934). 26545934
ERBB2 Y772_A775dup Advanced Solid Tumor resistant Lapatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) were resistant to Tykerb (lapatinib) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup Advanced Solid Tumor resistant Lapatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup were resistant to Tykerb (lapatinib) in culture (PMID: 31588020). 31588020
ERBB2 Y772_A775dup Advanced Solid Tumor resistant Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) were resistant to Tagrisso (osimertinib) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup Advanced Solid Tumor resistant Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup were resistant to Tagrisso (osimertinib) in culture (PMID: 31588020). 31588020
ERBB2 Y772_A775dup Advanced Solid Tumor resistant Tarloxotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup were resistant to Tarloxotinib (TRLX) in culture (PMID: 31588020). 31588020
ERBB2 Y772_A775dup lung cancer no benefit Gefitinib Preclinical Actionable In a preclinical study, bronchial epithelial cells expressing ERBB2 (HER2) Y772_A775dup (also referred to as A775_G776insYVMA) did not demonstrate sensitivity to Iressa (gefitinib) in culture (PMID: 26545934). 26545934
ERBB2 Y772_A775dup Advanced Solid Tumor conflicting Neratinib Preclinical - Cell culture Actionable In a preclinical study, Nerlynx (neratinib) inhibited growth of transformed cells expressing ERBB2 (HER2) Y772_A775dup (also referred to as ERBB2 A775_G776insYVMA) in culture (PMID: 28363995). 28363995
ERBB2 Y772_A775dup Advanced Solid Tumor conflicting Neratinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup were resistant to Nerlynx (neratinib) in culture (PMID: 31588020). 31588020
ERBB2 Y772_A775dup lung non-small cell carcinoma predicted - sensitive Afatinib Clinical Study Actionable In a retrospective analysis, Gilotrif (afatinib) treatment resulted in an objective response rate of 16% (5/31) in non-small cell lung cancer patients harboring ERBB2 (HER2) Y772_A775dup (reported as (A775_G776insYVMA) (PMID: 30527195). 30527195
ERBB2 Y772_A775dup urinary bladder cancer predicted - resistant Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease with a progression-free survival of 1.7 months in a patients with bladder cancer harboring ERBB2 (HER2) Y722_A775dup (PMID: 29420467; NCT01953926). 29420467
ERBB2 Y772_A775dup Advanced Solid Tumor resistant AZ5104 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) were resistant to AZ5104 in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup breast cancer sensitive Ado-trastuzumab emtansine + Poziotinib Preclinical - Cell culture Actionable In a preclinical study, addition of Poziotinib (HM781-36B) enhanced growth inhibition by Kadcyla (ado-trastuzumab emtansine) treatment in breast cancer cells expressing ERBB2 (HER2) Y772_A775dup in culture (PMID: 31588020). 31588020
ERBB2 Y772_A775dup lung non-small cell carcinoma no benefit Dacomitinib Clinical Study Actionable In a retrospective analysis, Vizimpro (dacomitinib) treatment resulted in an objective response rate of 0% (0/13) in non-small cell lung cancer patients harboring ERBB2 (HER2) Y772_A775dup (reported as (A775_G776insYVMA) (PMID: 30527195). 30527195
ERBB2 Y772_A775dup Advanced Solid Tumor predicted - sensitive Ganetespib Preclinical - Cell culture Actionable In a preclinical study, Ganetespib inhibited growth of transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as reported as A775_G776insYVMA) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup breast cancer sensitive Poziotinib Preclinical - Cell culture Actionable In a preclinical study, Poziotinib (HM781-36B) inhibited viability of breast cancer cells expressing ERBB2 (HER2) Y772_A775dup in culture (PMID: 31588020). 31588020
ERBB2 Y772_A775dup Advanced Solid Tumor conflicting Pyrotinib Preclinical - Cell culture Actionable In a preclinical study, Pyrotinib inhibited growth of transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup Advanced Solid Tumor conflicting Pyrotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y722_A755dup were resistant to Pyrotinib in culture (PMID: 31588020). 31588020
ERBB2 Y772_A775dup Advanced Solid Tumor predicted - sensitive Luminespib Preclinical - Cell culture Actionable In a preclinical study, Luminespib (AUY922) inhibited growth of transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as reported as A775_G776insYVMA) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup Her2-receptor negative breast cancer predicted - sensitive Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in complete response in one patient, and stable disease in 2 patient with Erbb2 (Her2) receptor negative (non-amplified) breast cancer harboring ERBB2 (HER2) Y772_A775dup (PMID: 29420467; NCT01953926). 29420467
ERBB2 Y772_A775dup Advanced Solid Tumor resistant Dacomitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup were resistant to Vizimpro (dacomitinib) in culture (PMID: 31588020). 31588020
ERBB2 Y772_A775dup Advanced Solid Tumor resistant Dacomitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) demonstrated decreased response to Vizimpro (dacomitinib) compared to Poziotinib (HM781-36B) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup lung non-small cell carcinoma predicted - sensitive Poziotinib Phase II Actionable In a Phase II trial, Poziotinib (HM781-36B) treatment resulted in a confirmed objective response rate of 42% (5/12) in patients with non-small cell lung cancer harboring ERBB2 (HER2) Y772_A775dup (n=9) or ERBB2 (HER2) G778_P780dup (n=3), with a median progression-free survival of 5.6 months (PMID: 31588020; NCT03066206). 31588020
ERBB2 Y772_A775dup lung non-small cell carcinoma predicted - sensitive Poziotinib Clinical Study Actionable In a retrospective analysis, Poziotinib (HM781-36B) treatment resulted in an objective response rate of 33% (1/3) in non-small cell lung cancer patients harboring ERBB2 (HER2) Y772_A775dup (reported as (A775_G776insYVMA) (PMID: 30527195). 30527195
ERBB2 Y772_A775dup Advanced Solid Tumor resistant Ibrutinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup were resistant to Imbruvica (ibrutinib) in culture (PMID: 31588020). 31588020
ERBB2 Y772_A775dup Advanced Solid Tumor sensitive Poziotinib Preclinical - Cell culture Actionable In a preclinical study, Poziotinib (HM781-36B) inhibited ERBB2 (HER2) phosphorylation and growth of a transformed cell line expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) in culture (PMID: 29686424). 29686424
ERBB2 Y772_A775dup Advanced Solid Tumor sensitive Poziotinib Preclinical - Cell culture Actionable In a preclinical study, Poziotinib (HM781-36B) inhibited survival of transformed cells expressing ERBB2 (HER2) Y772_A775dup in culture (PMID: 31588020). 31588020
ERBB2 Y772_A775dup Advanced Solid Tumor resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) were resistant to Tarceva (erlotinib) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup Advanced Solid Tumor resistant Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) demonstrated decreased response to Gilotrif (afatinib) compared to Poziotinib (HM781-36B) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup Advanced Solid Tumor resistant Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup were resistant to Gilotrif (afatinib) in culture (PMID: 31588020). 31588020
ERBB2 Y772_A775dup lung non-small cell carcinoma no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease in 5 patients and progressive disease in 4 patients with non-small cell lung cancer harboring ERBB2 (HER2) Y772_A775dup (PMID: 29420467; NCT01953926). 29420467
ERBB2 Y772_A775dup Advanced Solid Tumor resistant Tucatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) were resistant to Tucatinib (ARRY-380) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup lung adenocarcinoma conflicting Afatinib Case Reports/Case Series Actionable In a clinical study, a lung adenocarcinoma patient harboring ERBB2 Y772_A775dup (also referred to as A775_G776insYVMA and E740_A741insAYVM) achieved a partial response for 5 months following treatment with pulse Gilotrif (afatinib), however, a second patient harboring ERBB2 Y772_A775dup treated with pulse Gilotrif (afatinib) demonstrated progressive disease (PMID: 26964772). 26964772
ERBB2 Y772_A775dup Advanced Solid Tumor resistant Sapitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup were resistant to Sapitinib (AZD8931) in culture (PMID: 31588020). 31588020
ERBB2 Y772_A775dup lung non-small cell carcinoma no benefit Erlotinib Clinical Study Actionable In a retrospective analysis, Tarceva (erlotinib) treatment resulted in an objective response rate of 0% (0/1) in non-small cell lung cancer patients harboring ERBB2 (HER2) Y772_A775dup (reported as (A775_G776insYVMA) (PMID: 30527195). 30527195
ERBB2 Y772_A775dup lung cancer sensitive Poziotinib Preclinical Actionable In a preclinical study, Poziotinib (HM781-36B) induced regression of lung tumors in mouse models harboring ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA), with no signs of progression at 12 weeks (PMID: 29686424). 29686424
ERBB2 Y772_A775dup lung adenocarcinoma predicted - sensitive Poziotinib Phase II Actionable In a Phase II trial, Poziotinib (HM781-36B) treatment resulted in 1 partial response, 1 stable disease, and 1 progressive disease in 3 patients with lung adenocarcinoma harboring ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) (PMID: 30149884; NCT02979821). 30149884
ERBB2 Y772_A775dup lung non-small cell carcinoma sensitive Ado-trastuzumab emtansine + Poziotinib Preclinical - Pdx Actionable In a preclinical study, Poziotinib (HM781-36B) and Kadcyla (ado-trastuzumab emtansine) combination treatment resulted in sustained tumor regression in patient-derived xenograft models of non-small cell lung cancer harboring ERBB2 (HER2) Y772_A775dup (PMID: 31588020). 31588020
ERBB2 Y772_A775dup ERBB2 C805S Advanced Solid Tumor predicted - sensitive Luminespib Preclinical - Cell culture Actionable In a preclinical study, Luminespib (AUY922) inhibited growth of transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as reported as A775_G776insYVMA) and an acquired ERBB2 (HER2) C805S in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup ERBB2 C805S Advanced Solid Tumor resistant Pyrotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) and an acquired ERBB2 (HER2) C805S were resistant to Pyrotinib in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup ERBB2 C805S Advanced Solid Tumor resistant Tucatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) and an acquired ERBB2 (HER2) C805S were resistant to Tucatinib (ARRY-380) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup ERBB2 C805S Advanced Solid Tumor resistant Poziotinib Preclinical - Cell culture Actionable In a preclinical study, ERBB2 (HER2) C805S was identified as a secondary mutation in transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) that acquired resistance to Poziotinib (HM781-36B) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup ERBB2 C805S Advanced Solid Tumor resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) and an acquired ERBB2 (HER2) C805S were resistant to Tarceva (erlotinib) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup ERBB2 C805S Advanced Solid Tumor resistant Lapatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) and an acquired ERBB2 (HER2) C805S were resistant to Tykerb (lapatinib) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup ERBB2 C805S Advanced Solid Tumor resistant Neratinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing ERBB2 (HER2) Y772_A775dup (also referred to as A775_G776insYVMA) and ERBB2 (HER2) C805S demonstrated resistance to Nerlynx (neratinib) in culture (PMID: 28363995). 28363995
ERBB2 Y772_A775dup ERBB2 C805S Advanced Solid Tumor predicted - sensitive Ganetespib Preclinical - Cell culture Actionable In a preclinical study, Ganetespib inhibited growth of transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as reported as A775_G776insYVMA) and an acquired ERBB2 (HER2) C805S in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup ERBB2 C805S Advanced Solid Tumor resistant Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) and an acquired ERBB2 (HER2) C805S were resistant to Tagrisso (osimertinib) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup ERBB2 C805S Advanced Solid Tumor resistant AZ5104 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) and an acquired ERBB2 (HER2) C805S were resistant to AZ5104 in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup ERBB2 C805S Advanced Solid Tumor resistant Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing ERBB2 (HER2) Y772_A775dup (also referred to as A775_G776insYVMA) and ERBB2 (HER2) C805S demonstrated resistance to Gilotrif (afatinib) in culture (PMID: 28363995). 28363995
ERBB2 Y772_A775dup ERBB2 C805S Advanced Solid Tumor resistant Dacomitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing ERBB2 (HER2) C805S and ERBB2 (HER2) Y772_A775dup (also referred to as A775_G776insYVMA) demonstrated resistance to Vizimpro (dacomitinib) in culture (PMID: 28363995). 28363995
ERBB2 Y772_A775dup ERBB2 amp Her2-receptor positive breast cancer predicted - sensitive Neratinib Case Reports/Case Series Actionable In a clinical study, Nerlynx (neratinib) treatment resulted in partial response in 2 of 6 and disease stabilization in 4 of 6 breast cancer patients with ERBB2 (HER2) amplification and an ERBB2 (HER2) mutation, including stable disease in a patient harboring ERBB2 (HER2) Y772_A775dup (PMID: 30301790). 30301790