Submissions for variant NM_001374258.1(BRAF):c.1919T>A (p.Val640Glu) (rs113488022)

Total submissions: 35

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.
Clinical Genetics Karolinska University Hospital,Karolinska University Hospital	RCV000080903	SCV001450230	pathogenic	not provided	2014-07-11	criteria provided, single submitter	clinical testing
OMIM	RCV000067669	SCV000035247	pathogenic	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 stromal tumor	2014-10-02	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000067669	SCV000504249	pathogenic	Melanoma	2016-03-10	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000433305	SCV000504250	pathogenic	Lung carcinoma	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	Neoplasm of ovary	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	Colonic neoplasm	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
Pediatric Oncology, Johns Hopkins University	RCV001248834	SCV001147031	pathogenic	Nephroblastoma	2019-02-15	no assertion criteria provided	clinical testing
Investigational Cancer Therapeutics,MD Anderson Cancer Center	RCV001254874	SCV001424772	likely pathogenic	Malignant neoplastic disease		no assertion criteria provided	research
Department of Pathology and Laboratory Medicine,Sinai Health System	RCV000080903	SCV001550994	uncertain significance	not provided		no assertion criteria provided	clinical testing