Annotation Detail

Information
Associated Genes
ERBB2
Associated Variants
ERBB2 p.Tyr772_Ala775dup (p.Y772_A775dup) ( ENST00000541774.5, ENST00000269571.10, ENST00000445658.6, ENST00000406381.6, ENST00000584450.5, ENST00000584601.5 )
ERBB2 p.Tyr772_Ala775dup (p.Y772_A775dup) ( ENST00000269571.10, ENST00000406381.6, ENST00000445658.6, ENST00000541774.5, ENST00000584450.5, ENST00000584601.5 )
Associated Disease
lung adenocarcinoma
Source Database
CIViC Evidence
Description
A 55 year old heavily pretreated patient with equivocal HER2 overexpression (IHC2+ and no amplification in FISH) was found to have the HER2 YMVA kinase domain insertion. Afatinib monotherapy resulted in resolution of symptoms and 10 months before progressive disease. The patient was subsequently given trastuzumab with no response. The observed efficacy of afatinib against M774insAYVM, and studies reporting afatinib activity against other variants in the HER2 kinase domain, are cited by the authors as motivation for the arm of NCI-MATCH focusing on afatinib and activating HER2 mutations.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1045
Gene URL
https://civic.genome.wustl.edu/links/genes/20
Variant URL
https://civic.genome.wustl.edu/links/variants/414
Rating
4
Evidence Type
Predictive
Disease
Lung Adenocarcinoma
Evidence Direction
Supports
Drug
Afatinib
Evidence Level
C
Clinical Significance
Sensitivity/Response
Pubmed
26559459
Drugs
Drug NameSensitivitySupported
AfatinibSensitivitytrue