Gene Variant Detail

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Gene ERBB2
Variant L869R
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions 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).
Associated Drug Resistance Y

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Transcript NM_004448
gDNA chr17:g.39725161T>G
cDNA c.2606T>G
Protein p.L869R
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004448 chr17:g.39725161T>G c.2606T>G p.L869R RefSeq GRCh38/hg38
NM_001289937 chr17:g.39725161T>G c.2606T>G p.L869R 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 )
  • 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 L869R gain of function HER inhibitor (Pan) HER2 Inhibitor
ERBB2 T798I ERBB2 L869R
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ERBB2 L869R Advanced Solid Tumor resistant Sapitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) L869R were resistant to Sapitinib (AZD8931) in culture (PMID: 31588020). 31588020
ERBB2 L869R Advanced Solid Tumor sensitive Poziotinib Preclinical - Cell culture Actionable In a preclinical study, Poziotinib (HM781-36B) inhibited survival of transformed cells expressing ERBB2 (HER2) L755S in culture (PMID: 31588020). 31588020
ERBB2 L869R Advanced Solid Tumor sensitive Dacomitinib Preclinical - Cell culture Actionable In a preclinical study, Vizimpro (dacomitinib) inhibited survival of transformed cells expressing ERBB2 (HER2) L869R in culture (PMID: 31588020). 31588020
ERBB2 L869R Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, Gilotrif (afatinib) inhibited survival of transformed cells expressing ERBB2 (HER2) L869R in culture (PMID: 31588020). 31588020
ERBB2 L869R Advanced Solid Tumor resistant Lapatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) L869R were resistant to Tykerb (lapatinib) in culture (PMID: 31588020). 31588020
ERBB2 L869R Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) L869R were resistant to Tagrisso (osimertinib) in culture (PMID: 31588020). 31588020
ERBB2 L869R Advanced Solid Tumor sensitive Pyrotinib Preclinical - Cell culture Actionable In a preclinical study, Pyrotinib inhibited survival of transformed cells expressing ERBB2 (HER2) L869R in culture (PMID: 31588020). 31588020
ERBB2 L869R Advanced Solid Tumor sensitive Nazartinib Preclinical - Cell culture Actionable In a preclinical study, Nazartinib (EGF816) inhibited survival of transformed cells expressing ERBB2 (HER2) L869R in culture (PMID: 31588020). 31588020
ERBB2 L869R Advanced Solid Tumor sensitive Tarloxotinib Preclinical - Cell culture Actionable In a preclinical study, Tarloxotinib (TRLX) inhibited survival of transformed cells expressing ERBB2 (HER2) L869R in culture (PMID: 31588020). 31588020
ERBB2 L869R Advanced Solid Tumor resistant Ibrutinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) L869R were resistant to Imbruvica (ibrutinib) in culture (PMID: 31588020). 31588020
ERBB2 L869R breast cancer sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, Gilotrif (afatinib) inhibited ERBB2 (HER2) phosphorylation and growth of transformed breast epithelial cells expressing ERBB2 (HER2) L869R in culture (PMID: 28274957). 28274957
ERBB2 L869R Her2-receptor negative breast cancer predicted - sensitive Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in partial response with a progression-free survival of 3.6 months in a patient with Erbb2 (Her2) receptor negative (non-amplified) breast cancer harboring ERBB2 (HER2) L869R (PMID: 29420467; NCT01953926). 29420467
ERBB2 L869R breast cancer sensitive Neratinib Phase II Actionable In a Phase II trial, Nerlynx (neratinib) demonstrated activity in metastatic breast cancer patients harboring ERBB2 (HER2) mutations, resulting in a clinical benefit rate of 31% (5/16), with 1 complete response, 1 partial response, and 3 patients achieving stable disease for 24 weeks or more, which included a patient harboring ERBB2 (HER2) L869R (PMID: 28679771). 28679771
ERBB2 L869R breast cancer sensitive Neratinib Preclinical - Cell culture Actionable In a preclinical study, Nerlynx (neratinib) inhibited ERBB2 (HER2) phosphorylation and growth of transformed breast epithelial cells expressing ERBB2 (HER2) L869R in culture (PMID: 28274957). 28274957
ERBB2 L869R colorectal adenocarcinoma predicted - resistant Lapatinib + Trastuzumab Case Reports/Case Series Actionable In a clinical case study, a colorectal carcinoma patient who initially achieved stable disease following treatment with Tykerb (lapatinib) and Herceptin (trastuzumab) developed secondary resistance, presenting with a brain metastasis, and ERBB2 (HER2) L869R was identified in the brain lesion (PMID: 29941010). 29941010
ERBB2 L869R breast cancer resistant Lapatinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed breast cancer cells over expressing ERBB2 (HER2) L869R were resistant to Tykerb (lapatinib) in culture, formed tumors and metastasized readily in xenograft animal models (PMID: 27900369). 27900369
ERBB2 L869R lung adenocarcinoma predicted - resistant Lapatinib Case Reports/Case Series Actionable In a clinical case study, ERBB2 (HER2) L869R was identified in the lymph node metastasis from a lung adenocarcinoma patient that progressed on Tykerb (lapatinib) therapy (PMID: 27900369). 27900369