Annotation Detail

Information
Associated Genes
BRAF
Associated Variants
BRAF p.Gly509Ala (p.G509A) ( ENST00000288602.11, ENST00000496384.7, ENST00000644969.2, ENST00000646891.2 )
BRAF p.Gly509Ala (p.G509A) ( ENST00000288602.11, ENST00000496384.7, ENST00000644969.2, ENST00000646891.2 )
Associated Disease
cancer
Source Database
CIViC Evidence
Description
The phase 2a MyPathway study assigned patients with HER2, EGFR, BRAF or SHH alterations to treatment with pertuzumab plus trastuzumab, erlotinib, vemurafenib, or vismodegib, respectively. Of 26 patients with BRAF V600E mutations, objective responses were seen in 12 patients (46%; 95% CI, 27% to 67%). Only one of 23 patients (4%; 95% CI, 0% to 22%) with other non-V600 BRAF mutations had a PR (pancreas cancer with a CUX1-BRAF fusion). Nonresponding BRAF mutations included: K601E (n = 6), G464V (n = 2), G469A (n = 2), G496A (n = 2), N581S (n = 2), and one each for G466V, G596R, G606E, L597Q, P731T, intron 9 rearrangement, intron 10 rearrangement, and MACF1- and WASFL-BRAF fusion.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/5965
Gene URL
https://civic.genome.wustl.edu/links/genes/5
Variant URL
https://civic.genome.wustl.edu/links/variants/992
Rating
2
Evidence Type
Predictive
Disease
Cancer
Evidence Direction
Does Not Support
Drug
Vemurafenib
Evidence Level
C
Clinical Significance
Sensitivity/Response
Pubmed
29320312
Drugs
Drug NameSensitivitySupported
VemurafenibSensitivityfalse