ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.1798_1799delinsAA (p.Val600Lys) (rs121913227)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CIViC knowledgebase,Washington University School of Medicine RCV001030021 SCV001192825 drug response Vemurafenib-Cobimetinib Response criteria provided, single submitter curation BRAF V600K mutant melanoma is sensitive to vemurafenib and cobimetinib combination therapy. Vemurafenib and cobimentinb is an FDA approved and NCCN Category 1 first line treatment for BRAF V600K 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. BRAF-targeted therapy are recommend as Category 2A treatment options in second-line or later treatment 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 RCV001030022 SCV001192826 drug response Trametinib-Dabrafenib Response criteria provided, single submitter curation BRAF V600K 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 the less common BRAF V600K 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.
Database of Curated Mutations (DoCM) RCV000422502 SCV000504266 pathogenic Melanoma 2015-07-14 no assertion criteria provided literature only
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001355295 SCV001550139 uncertain significance not provided no assertion criteria provided clinical testing

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