ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.1799T>A (p.Val600Glu) (rs113488022)

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Total submissions: 31
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000080903 SCV000112810 pathogenic not provided 2013-10-08 criteria provided, single submitter clinical testing
CIViC knowledgebase,Washington University School of Medicine RCV001030018 SCV001192822 drug response Trametinib-Dabrafenib Response criteria provided, single submitter curation BRAF V600E mutant melanoma is sensitive to dabrafenib and trametinib combination therapy. Combination treatment of BRAF inhibitor dabrafenib and MEK inhibitor trametinib is recommended for adjuvant treatment of stage III or recurrent melanoma with BRAF V600E mutation detected by the approved THxID kit, as well as first line treatment for metastatic melanoma. The treatments are FDA approved and NCCN guidelines recommend these treatments as category 1 based on studies including the Phase III COMBI-V, COMBI-D and COMBI-AD Trials. Combination therapy is now recommended above BRAF inhibitor monotherapy. Dabrafenib and trametinib are recommend as NCCN Category 2A for second line therapy in metastatic melanoma due to lack of clear Phase III trial data for this use case. Cutaneous squamous-cell carcinoma and keratoacanthoma occur at lower rates with combination therapy than with BRAF inhibitor alone.
CIViC knowledgebase,Washington University School of Medicine RCV001030020 SCV001192824 drug response Vemurafenib-Cobimetinib Response criteria provided, single submitter curation BRAF V600E mutant melanoma is sensitive to vemurafenib and cobimetinib combination therapy. Vemurafenib and cobimetinib combination is an FDA approved and NCCN Category 1 first line treatment for BRAF V600E mutant metastatic melanoma based on clinical data including the Phase III coBRIM trial. NCCN guidelines recommend combination BRAF/MEK inhibitor therapy over BRAF inhibitor monotherapy in this treatment context. Vemurafenib and cobimetinib combination is recommend as Category 2A treatment in second-line or later contexts, and it is recommended to use treatment options different from those used with the patient during first-line therapy. The cobas 4800 BRAF V600 Mutation Test is approved as an FDA companion test for Cotellic (cobimetinib) in combination with Zelboraf (vemurafenib).
CIViC knowledgebase,Washington University School of Medicine RCV001030023 SCV001192827 other Colorectal cancer criteria provided, single submitter curation BRAF V600E indicates poor prognosis in advanced colorectal cancer. BRAF V600E was associated with worse prognosis in Phase II and III colorectal cancer, with a stronger effect in MSI-Low or MSI-Stable tumors. In metastatic CRC, V600E was associated with worse prognosis, and meta-analysis showed BRAF mutation in CRC associated with multiple negative prognostic markers. NCCN Guidelines state that that mutations in BRAF are a strong prognostic marker, and recommend BRAF genotyping of either primary or metastatic tumor tissue at diagnosis of stage IV disease.
OMIM RCV000067669 SCV000035247 pathogenic Cutaneous melanoma 2014-09-04 no assertion criteria provided literature only
OMIM RCV000014992 SCV000035248 pathogenic Carcinoma of colon 2014-09-04 no assertion criteria provided literature only
OMIM RCV000014993 SCV000035249 pathogenic Papillary thyroid carcinoma 2014-09-04 no assertion criteria provided literature only
OMIM RCV000014994 SCV000035250 pathogenic Astrocytoma, low-grade, somatic 2014-09-04 no assertion criteria provided literature only
OMIM RCV000022677 SCV000043966 pathogenic Germ cell tumor, nonseminomatous 2014-09-04 no assertion criteria provided literature only
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000037936 SCV000061601 pathogenic Non-small cell lung cancer 2009-05-29 no assertion criteria provided clinical testing
GeneReviews RCV000208763 SCV000264636 pathogenic Cardio-facio-cutaneous syndrome 2016-03-03 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440540 SCV000504248 pathogenic Gastrointestinal stroma tumor 2014-10-02 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000067669 SCV000504249 pathogenic Cutaneous melanoma 2016-03-10 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433305 SCV000504250 pathogenic Lung cancer 2014-10-02 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443745 SCV000504251 pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425847 SCV000504252 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432628 SCV000504253 pathogenic Ovarian Neoplasms 2014-10-02 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443448 SCV000504254 likely pathogenic Neoplasm 2016-05-13 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425166 SCV000504255 likely pathogenic Brainstem glioma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000435441 SCV000504256 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000417746 SCV000504257 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424470 SCV000504258 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000037936 SCV000504259 not provided Non-small cell lung cancer 2016-03-10 no assertion provided literature only
Database of Curated Mutations (DoCM) RCV000420614 SCV000504260 likely pathogenic Neoplasm of the colon 2015-07-14 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430562 SCV000504261 likely pathogenic Multiple myeloma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440802 SCV000504262 likely pathogenic Papillary renal cell carcinoma, sporadic 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000014993 SCV000504263 not provided Papillary thyroid carcinoma 2016-03-10 no assertion provided literature only
Database of Curated Mutations (DoCM) RCV000429915 SCV000504264 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Yale Center for Mendelian Genomics,Yale University RCV000662278 SCV000784606 pathogenic Cystic epithelial invagination containing papillae lined by columnar epithelium 2015-05-07 no assertion criteria provided literature only
Arin Greene Laboratory,Boston Children's Hospital, Harvard Medical School RCV000860020 SCV000992587 pathogenic Cerebral arteriovenous malformation no assertion criteria provided research
Xiao lab, Department of Pathology, Memorial Sloan Kettering Cancer Center RCV000430562 SCV001132084 likely pathogenic Multiple myeloma 2019-08-31 no assertion criteria provided clinical testing

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