Gene Variant Detail

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Gene ERBB2
Variant D769Y
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions 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).
Associated Drug Resistance Y

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Transcript NM_004448
gDNA chr17:g.39724008G>T
cDNA c.2305G>T
Protein p.D769Y
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_001289937 chr17:g.39724008G>T c.2305G>T p.D769Y RefSeq GRCh38/hg38
NM_004448 chr17:g.39724008G>T c.2305G>T p.D769Y RefSeq GRCh38/hg38

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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 )
  • 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 Protein Effect Treatment Approaches
ERBB2 D769Y gain of function HER inhibitor (Pan) HER2 Inhibitor
ERBB2 D769Y ERBB2 amp
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ERBB2 D769Y breast cancer sensitive Lapatinib Preclinical Actionable In a preclinical study, transformed human breast cell lines expressing ERBB2 D769Y reverted to normal morphology in culture upon Tykerb (lapatinib) treatment (PMID: 23220880). 23220880
ERBB2 D769Y Advanced Solid Tumor sensitive Poziotinib Preclinical - Cell culture Actionable In a preclinical study, Poziotinib (HM781-36B) inhibited survival of transformed cells expressing ERBB2 (HER2) D769Y in culture (PMID: 31588020). 31588020
ERBB2 D769Y Advanced Solid Tumor resistant Sapitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) D769Y were resistant to Sapitinib (AZD8931) in culture (PMID: 31588020). 31588020
ERBB2 D769Y Advanced Solid Tumor resistant Lapatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) D769Y were resistant to Tykerb (lapatinib) in culture (PMID: 31588020). 31588020
ERBB2 D769Y breast cancer sensitive Neratinib Preclinical Actionable In a preclinical study, transformed human breast cell lines expressing ERBB2 (HER2) D769Y reverted to normal morphology in culture upon Nerlynx (neratinib) treatment (PMID: 23220880). 23220880
ERBB2 D769Y Advanced Solid Tumor sensitive Nazartinib Preclinical - Cell culture Actionable In a preclinical study, Nazartinib (EGF816) inhibited survival of transformed cells expressing ERBB2 (HER2) D769Y in culture (PMID: 31588020). 31588020
ERBB2 D769Y Advanced Solid Tumor sensitive Pyrotinib Preclinical - Cell culture Actionable In a preclinical study, Pyrotinib inhibited survival of transformed cells expressing ERBB2 (HER2) D769Y in culture (PMID: 31588020). 31588020
ERBB2 D769Y breast cancer sensitive Trastuzumab Preclinical Actionable In a preclinical study, transformed human breast cell lines expressing ERBB2 D769Y reverted to normal morphology in culture upon Herceptin (trastuzumab) treatment (PMID: 23220880). 23220880
ERBB2 D769Y gastroesophageal junction adenocarcinoma 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 1.9 months in a patient with gastroesophageal cancer harboring ERBB2 (HER2) D769Y (PMID: 29420467; NCT01953926). 29420467
ERBB2 D769Y 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 1.4 months in a patient with bladder cancer harboring both ERBB2 (HER2) D769Y (PMID: 29420467; NCT01953926). 29420467
ERBB2 D769Y Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, Gilotrif (afatinib) inhibited survival of transformed cells expressing ERBB2 (HER2) D769Y in culture (PMID: 31588020). 31588020
ERBB2 D769Y Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, Tagrisso (osimertinib) inhibited survival of transformed cells expressing ERBB2 (HER2) D769Y in culture (PMID: 31588020). 31588020
ERBB2 D769Y Advanced Solid Tumor sensitive Tarloxotinib Preclinical - Cell culture Actionable In a preclinical study, Tarloxotinib (TRLX) inhibited survival of transformed cells expressing ERBB2 (HER2) D769Y in culture (PMID: 31588020). 31588020
ERBB2 D769Y Advanced Solid Tumor sensitive Ibrutinib Preclinical - Cell culture Actionable In a preclinical study, Imbruvica (ibrutinib) inhibited survival of transformed cells expressing ERBB2 (HER2) D769Y in culture (PMID: 31588020). 31588020
ERBB2 D769Y Advanced Solid Tumor sensitive Dacomitinib Preclinical - Cell culture Actionable In a preclinical study, Vizimpro (dacomitinib) inhibited survival of transformed cells expressing ERBB2 (HER2) D769Y in culture (PMID: 31588020). 31588020
ERBB2 D769Y ERBB2 amp Her2-receptor positive breast cancer 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) D769Y, and Nerlynx (neratinib) inhibited tumor growth in a breast cancer patient-derived xenograft (PDX) model with ERBB2 (HER2) amplification and ERBB2 (HER2) D769Y (PMID: 30301790). 30301790
ERBB2 D769Y ERBB2 amp Her2-receptor positive breast cancer resistant Trastuzumab Preclinical - Pdx Actionable In a preclinical study, a breast cancer patient-derived xenograft (PDX) model with ERBB2 (HER2) amplification and ERBB2 D769Y was refractory to treatment with Herceptin (trastuzumab) (PMID: 30301790). 30301790
ERBB2 D769Y ERBB2 amp Her2-receptor positive breast cancer resistant Lapatinib Preclinical - Pdx Actionable In a preclinical study, a breast cancer patient-derived xenograft (PDX) model with ERBB2 (HER2) amplification and ERBB2 D769Y was refractory to treatment with Tykerb (lapatinib) (PMID: 30301790). 30301790