Gene Variant Detail

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Gene BRAF
Variant V600X
Impact List missense
Protein Effect unknown
Gene Variant Descriptions BRAF V600X indicates any BRAF missense mutation that results in replacement of the valine (V) at amino acid 600 by a different amino acid. BRAF V600 mutations are hotspot mutations that often result in increased Braf kinase activity (PMID: 15035987).
Associated Drug Resistance
Category Variants Paths

BRAF mutant BRAF V600X

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Transcript NM_004333.6
gDNA chr7:g.140753335_140753337
cDNA c.1798_1800
Protein p.V600
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004333.5 chr7:g.140753335_140753337 c.1798_1800 p.V600 RefSeq GRCh38/hg38
NM_001378468.1 chr7:g.140753335_140753337 c.1798_1800 p.V600 RefSeq GRCh38/hg38
NM_004333.6 chr7:g.140753335_140753337 c.1798_1800 p.V600 RefSeq GRCh38/hg38
NM_001378474.1 chr7:g.140753335_140753337 c.1798_1800 p.V600 RefSeq GRCh38/hg38
XM_005250045 chr7:g.140753335_140753337 c.1798_1800 p.V600 RefSeq GRCh38/hg38
NM_004333 chr7:g.140753335_140753337 c.1798_1800 p.V600 RefSeq GRCh38/hg38
NM_001354609.1 chr7:g.140753335_140753337 c.1798_1800 p.V600 RefSeq GRCh38/hg38
NM_001354609.2 chr7:g.140753335_140753337 c.1798_1800 p.V600 RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF V600X melanoma sensitive Binimetinib Phase II Actionable In a Phase II trial, Binimetinib (MEK162) treatment resulted in a partial response in 20% (8/41) of melanoma patients harboring BRAF V600 mutations, including V600E (33/41), V600K (5/41), and V600R (1/41) (PMID: 23414587; NCT01320085). 23414587
BRAF V600X melanoma sensitive Cobimetinib + Vemurafenib Phase III Actionable In a Phase III trial, combination treatment with Zelboraf (vemurafenib) and Cotellic (cobimetinib) resulted in an improved progression-free survival of 12.3 months compared to 7.2 months with Zelboraf (vemurafenib) alone among patients with BRAF V600-mutated metastatic melanoma (PMID: 27480103; NCT01689519). 27480103
BRAF V600X skin melanoma sensitive Dabrafenib Guideline Actionable Tafinlar (dabrafenib) therapy is included in guidelines for patients with unresectable or metastatic cutaneous melanoma harboring BRAF V600 activating mutations, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org). detail...
BRAF V600X skin melanoma sensitive Vemurafenib Guideline Actionable Zelboraf (vemurafenib) therapy is included in guidelines for patients with unresectable or metastatic cutaneous melanoma harboring BRAF V600 activating mutations, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org). detail...
BRAF V600X melanoma sensitive Dabrafenib + Trametinib Phase Ib/II Actionable In a Phase I/II clinical trial, patients with BRAF V600 mutant melanoma (n=78) treated with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) had a median overall survival of greater than 2 years (PMID: 26811525). 26811525
BRAF V600X colorectal cancer no benefit Vemurafenib Case Reports/Case Series Actionable In a Phase II trial, treatment with Zelboraf (vemurafenib) in colorectal cancer patients with BRAF V600 mutations did not result in clinical benefit, with no patients achieving response, and 50% (5/10) demonstrating progressive disease (PMID: 26287849; NCT01524978). 26287849
BRAF V600X colorectal cancer sensitive Cetuximab + Vemurafenib Phase II Actionable In a Phase II trial, treatment with the combination of Zelboraf (vemurafenib) and Erbitux (cetuximab) resulted in an overall response rate of 4% (1/26), stable disease in 69% (18/26), and a median progression-free survival of 3.7 months in patients with BRAF V600-mutant colorectal cancer (PMID: 26287849; NCT01524978). 26287849
BRAF V600X thyroid cancer predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a Phase II trial, treatment with Zelboraf (vemurafenib) resulted in an overall response rate of 29% (2/7), with 1 complete response and 1 partial response, in patients with anaplastic thyroid cancer patients with BRAF V600 mutations (PMID: 26287849; NCT01524978). 26287849
BRAF V600X cholangiocarcinoma predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a Phase II trial, treatment with Zelboraf (vemurafenib) resulted in partial response in 12% (1/8) and stable disease in 50% (4/8) of cholangiocarcinoma patients with BRAF V600 mutations (PMID: 26287849; NCT01524978). 26287849
BRAF V600X melanoma sensitive Trametinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the combination of Mekinist (trametinib) and Zelboraf (vemurafenib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). 24265152
BRAF V600X melanoma sensitive Selumetinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the combination of Selumetinib (AZD6244) and Zelboraf (vemurafenib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). 24265152
BRAF V600X melanoma sensitive Buparlisib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the combination of Buparlisib (BKM120) and Zelboraf (vemurafenib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). 24265152
BRAF V600X melanoma sensitive Buparlisib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Buparlisib (BKM120) and Mekinist (trametinib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). 24265152
BRAF V600X melanoma sensitive Buparlisib + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Buparlisib (BKM120) and Koselugo (selumetinib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). 24265152
BRAF V600X melanoma sensitive MK2206 + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the combination of MK2206 and Zelboraf (vemurafenib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). 24265152
BRAF V600X melanoma sensitive MK2206 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of MK2206 and Mekinist (trametinib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). 24265152
BRAF V600X melanoma sensitive ASN003 Preclinical - Pdx Actionable In a preclinical study, melanoma patient derived xenograft (PDX) model harboring a BRAF V600 mutation demonstrated antitumor activity when treated with ASN003 (J Clin Oncol 35, 2017 (suppl; abstr e14102)). detail...
BRAF V600X melanoma sensitive Dabrafenib + KRT-232 + Trametinib Phase I Actionable In a Phase I trial, the combination therapy of KRT-232 (AMG 232), Mekinist (trametinib), and Tafinlar (dabrafenib) in 6 patients with metastatic cutaneous melanoma harboring a BRAF V600 mutation resulted in 4 patients with a partial response and 2 patients with stable disease, and of the 6 patients, all experienced tumor reduction (J Clin Oncol 35, 2017 (suppl; abstr 2575)). detail...
BRAF V600X melanoma sensitive Atezolizumab + Cobimetinib + Vemurafenib Phase Ib/II Actionable In a Phase Ib trial, the combination therapy of Tecentriq (atezolizumab), Zelboraf (vemurafenib), and Cotellic (cobimetinib) in patients with metastatic melanoma harboring a BRAF V600 mutation resulted in a best objective response rate of 71.8% (28/39), with a complete response in 20.5% (8/39), a median progression-free survival of 12.9 months, a median overall survival not yet reached, and median duration of confirmed response of 17.4 months (PMID: 31171876; NCT01656642). detail... 31171876
BRAF V600X melanoma sensitive Atezolizumab + Cobimetinib + Vemurafenib FDA approved Actionable In a Phase III trial (IMspire150) that supported FDA approval, addition of Tecentriq (atezolizumab) to Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy significantly improved progression-free survival (15.1 vs 10.6 months, HR=0.78, p=0.025) compared to control in patients with advanced or metastatic melanoma harboring BRAF V600 mutations (PMID: 32534646; NCT02908672). 32534646 detail...
BRAF V600X lung non-small cell carcinoma sensitive Dabrafenib + Trametinib Guideline Actionable The combination of Tafinlar (dabrafenib) and Mekinist (trametinib) is included in guidelines as first-line therapy for patients with metastatic non-small cell lung cancer harboring a BRAF V600 mutation, or as subsequent therapy in patients harboring BRAF V600 mutations that have not received prior BRAF/MEK inhibitor therapy (PMID: 30285222; ESMO.org). detail... 30285222
BRAF V600X melanoma sensitive Atezolizumab + Vemurafenib Phase Ib/II Actionable In a Phase Ib trial, the combination therapy of Tecentriq (atezolizumab) and Zelboraf (vemurafenib) in patients with metastatic melanoma harboring a BRAF V600 mutation resulted in a best objective response rate of 76.5% (13/17), with a complete response in 17.6% (3/17), a median progression-free survival of 10.9 months, a median overall survival of 46.2 months, and median duration of confirmed response of 10.6 months (PMID: 31171876; NCT01656642). 31171876
BRAF V600X skin melanoma sensitive Cobimetinib + Vemurafenib Guideline Actionable BRAF inhibitor plus MEK inhibitor combination therapy, such as Cotellic (cobimetinib) plus Zelboraf (vemurafenib), is included in guidelines for cutaneous melanoma patients with unresectable or metastatic disease harboring a BRAF V600 mutation (PMID: 31566661; ESMO.org). 31566661 detail...
BRAF V600X skin melanoma sensitive Cobimetinib + Vemurafenib Guideline Actionable Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy is included in guidelines as a second-line or subsequent therapy for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 activating mutation (NCCN.org). detail...
BRAF V600X skin melanoma sensitive Dabrafenib + Trametinib Guideline Actionable BRAF inhibitor plus MEK inhibitor combination therapy, such as Tafinlar (dabrafenib) plus Mekinist (trametinib), is included in guidelines for cutaneous melanoma patients with unresectable or metastatic disease harboring a BRAF V600 mutation (PMID: 31566661; ESMO.org). 31566661 detail...
BRAF V600X skin melanoma sensitive Dabrafenib + Trametinib Guideline Actionable Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines as neoadjuvant or adjuvant therapy for stage III disease and as second-line or subsequent therapy for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 mutation (NCCN.org). detail...
BRAF V600X Advanced Solid Tumor predicted - sensitive Dabrafenib Phase I Actionable In a Phase I trial (BRF116013), Tafinlar (dabrafenib) treatment was well tolerated and demonstrated preliminary efficacy, resulted in a median duration of treatment of 75.6 week in pediatric patients with BRAF V600-mutant advanced solid tumors, including low-grade (n=15) and high-grade (n=8) gliomas, Langerhans cell histiocytosis (n=2), neuroblastoma (n=1), and papillary thyroid cancer (n=1) (PMID: 31506385; NCT01677741). 31506385
BRAF V600X low grade glioma predicted - sensitive Dabrafenib Phase Ib/II Actionable In a Phase I/II trial, Tafinlar (dabrafenib) treatment was well tolerated and demonstrated preliminary efficacy, resulted in an objective response rate of 44% (14/32, 1 complete response, 13 partial response) and a disease control rate of 78% (25/32), with a median duration of response of 26 months in pediatric patients with BRAF V600-mutant low-grade gliomas (PMID: 31811016; NCT01677741). 31811016
BRAF V600X ganglioglioma predicted - sensitive Dabrafenib Case Reports/Case Series Actionable In a Phase I/II trial, Tafinlar (dabrafenib) treatment resulted in a partial response in a pediatric patient with BRAF V600-mutant ganglioglioma (PMID: 31811016; NCT01677741). 31811016
BRAF V600X lung non-small cell carcinoma predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a Phase II trial, treatment with Zelboraf (vemurafenib) resulted in an overall response rate of 42% (8/19, 8 partial responses) in patients with non-small cell lung cancer harboring BRAF V600 mutations, with a median progression-free survival of 7.3 months (PMID: 26287849; NCT01524978}. 26287849
BRAF V600X lung non-small cell carcinoma predicted - sensitive Vemurafenib Phase II Actionable In a Phase II trial, Zelboraf (vemurafenib) treatment resulted in a objective response rate of 44.8% (43/96), median duration of response of 6.4 months, median progression-free survival of 5.2 months, and median overall survival of 10 months in non-small cell lung cancer patients with BRAF V600 mutations (PMID: 31959346; NCT02304809). 31959346
BRAF V600X Advanced Solid Tumor predicted - sensitive Lifirafenib Phase I Actionable In a Phase I trial, Lifirafenib (BGB-283) treatment demonstrated safety and resulted in partial response (PR) in 15.1% (8/53) of advanced solid tumor patients harboring a BRAF mutation, including 5 patients with BRAF V600E/K-mutant melanoma, 2 patients with BRAF V600E-mutant thyroid cancer, and 1 patient with BRAF V600E-mutant low-grade serous ovarian carcinoma, complete response in 1.9% (1/53), in a patient with melanoma, and stable disease in 50.9% (27/53) (PMID: 32182156; NCT02610361). 32182156
BRAF V600X skin melanoma sensitive Binimetinib + Encorafenib Guideline Actionable BRAF inhibitor plus MEK inhibitor combination therapy, such as Mektovi (binimetinib) plus Braftovi (encorafenib), is included in guidelines for cutaneous melanoma patients with unresectable or metastatic disease harboring a BRAF V600 mutation (PMID: 31566661; ESMO.org). 31566661 detail...
BRAF V600X skin melanoma sensitive Binimetinib + Encorafenib Guideline Actionable Mektovi (binimetinib) and Braftovi (encorafenib) combination therapy is included in guidelines as a second-line or subsequent therapy for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 activating mutation (NCCN.org). detail...
BRAF V600X melanoma predicted - sensitive Dabrafenib + Spartalizumab + Trametinib Phase III Actionable In a Phase III trial (COMBI-i), the combination of Tafinlar (dabrafenib), Mekinist (trametinib), and Spartalizumab (PDR001) resulted in an objective response rate of 78% (28/36, 16 complete, 12 partial), disease control rate of 94% (34/36), and median progression-free survival of 23 months in patients with BRAF V600-mutant metastatic melanoma, including 29 patients (81%) harboring BRAF V600E and 4 patients (11%) harboring BRAF V600K (PMID: 33020648; NCT02967692). 33020648
BRAF V600X melanoma predicted - sensitive Binimetinib + Encorafenib + Pembrolizumab Phase I Actionable In a Phase I trial (IMMU-Target), Mektovi (binimetinib), Braftovi (encorafenib), and Keytruda (pembrolizumab) demonstrated safety and preliminary efficacy in treatment naive patients with advanced melanoma harboring BRAF V600 mutations, resulting in an overall response rate of 64% (9/14), with a 12-month progression-free survival rate of 37.5% (n=8) and 60% (n=6) at the two tested dose levels, respectively (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 9532; NCT02902042). detail...
BRAF V600X melanoma predicted - sensitive Dabrafenib + Nivolumab + Trametinib Phase II Actionable In a Phase II trial, combination of Tafinlar (dabrafenib), Mekinist (trametinib), and Opdivo (nivolumab) resulted in an objective response rate (ORR) of 92% (24/27, 3 CR, 21 PR) in patients with MEK inhibitor-naive, BRAF V600-mutated melanoma, with a median progression-free survival of 8.5 mos, ORR was 88% (14/16) and 100% (10/10) in PD1 refractory or naive patients, 57% (4/7) of patients with brain metastasis achieved intracranial response (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 9520; NCT02910700). detail...
BRAF V600X Advanced Solid Tumor predicted - sensitive Belvarafenib + Cobimetinib Phase I Actionable In a Phase Ib trial, combination treatment with Belvarafenib (HM95573) and Cotellic (cobimetinib) was well-tolerated and demonstrated safety, and led to a confirmed partial response in 33.3% (3/9) solid tumor patients harboring BRAF V600 mutations (Annals of Oncology 32 (2021): S595; NCT03284502). detail...
BRAF V600X Advanced Solid Tumor predicted - sensitive PLX8394 Phase Ib/II Actionable In a Phase I/II trial, PLX8394 treatment resulted in a partial response in 39% (9/23) of patients with MAPK inhibitor-naive advanced solid tumors (excluding colorectal cancer) harboring BRAF V600X with a median duration of response of 32 months, and resulted in a partial response in 18% (3/17) and stable disease in 29% of patients previously treated with a MAPK inhibitor (J Clin Oncol 41, 2023 (suppl 16; abstr 3006); NCT02428712). detail...
BRAF V600X low grade glioma predicted - sensitive Trametinib Phase Ib/II Actionable In a Phase I/II trial, Mekinist (trametinib) treatment demonstrated a manageable safety profile in pediatric patients with BRAF V600-mutant low grade glioma, and resulted in an objective response rate of 15.4% (2/13, all partial responses), a clinical benefit rate of 61.5% (8/13), a median progression-free survival of 16.4 months, and median duration of response not reached (PMID: 36375115; NCT02124772). 36375115
BRAF V600X low grade glioma predicted - sensitive Dabrafenib + Trametinib Phase Ib/II Actionable In a Phase I/II trial, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment demonstrated a manageable safety profile in pediatric patients with BRAF V600-mutant low-grade glioma, and resulted in an objective response rate of 25% (9/36, all partial responses), a clinical benefit rate of 88.9% (32/36), a median duration of response of 33.6 months, and a median progression-free survival of 36.9 months (PMID: 36375115; NCT02124772). 36375115
BRAF V600X melanoma predicted - sensitive Ipilimumab + Nivolumab Clinical Study - Cohort Actionable In a retrospective analysis, melanoma patients harboring BRAF V600 mutations (V600E/K/R/D or V600_K601delinsE) treated with the combination of Yervoy (ipilimumab) and Opdivo (nivolumab) demonstrated significantly improved median progression-free survival (10.1 vs 5.2 months; P=0.0057) and median overall survival (not reached vs 16.9 months; P<0.0001) compared to patients without BRAF V600 mutations (PMID: 36130145). 36130145
BRAF V600X melanoma predicted - sensitive Dabrafenib + Hydroxychloroquine + Trametinib Phase Ib/II Actionable In a Phase I/II trial (BAMM), the combination of Tafinlar (dabrafenib), Mekinist (trametinib), and Plaquenil (hydroxychloroquine sulfate) resulted in a 1-year progression-free survival (PFS) rate of 48.2%, a median PFS of 11.2 mo, a response rate (RR) of 85% (29/34, 14 complete, 15 partial responses), and median overall survival (OS) of 26.5 mo in patients with advanced BRAF V600-mutant melanoma, RR, mPFS, and OS were 88%, 7.3, and 22 mo in patients with elevated LDH (n=16) (PMID: 35022320; NCT02257424). 35022320
BRAF V600X Advanced Solid Tumor predicted - sensitive ABM-1310 Phase I Actionable In a Phase I trial, ABM-1310 treatment was tolerated and demonstrated preliminary efficacy in patients with advanced solid tumors harboring BRAF V600X, resulting in 2 partial responses (1 pleomorphic xanthroastrocytoma, 1 glioblastoma) and 8 stable diseases among 16 evaluable patients (J Clin Oncol 41, 2023 (suppl 16; abstr 3098); NCT04190628). detail...
BRAF V600X melanoma predicted - sensitive ABM-1310 + Cobimetinib Case Reports/Case Series Actionable In a Phase I trial, the combination of ABM-1310 and Cotellic (cobimetinib) was tolerated and demonstrated preliminary efficacy in patients with advanced solid tumors harboring BRAF V600X, resulting in 1 partial response in a patient with melanoma and 1 stable disease among 3 evaluable patients (J Clin Oncol 41, 2023 (suppl 16; abstr 3098); NCT04190628). detail...
BRAF V600X colorectal cancer predicted - sensitive Tunlametinib + Vemurafenib Phase I Actionable In a Phase I trial, the combination of Tunlametinib (HL-085) and Zelboraf (vemurafenib) demonstrated safety and resulted in an objective response rate of 25.0% (6/24), a median duration of response of 5.5 months, and a median progression free survival of 6.2 months in patients with advanced colorectal cancer harboring a BRAF V600 mutation (Ann Oncol (2023) 34 (suppl_2): S790; NCT03781219). detail...
BRAF V600X lung non-small cell carcinoma predicted - sensitive Tunlametinib + Vemurafenib Phase I Actionable In a Phase I trial, the combination of Tunlametinib (HL-085) and Zelboraf (vemurafenib) demonstrated safety and resulted in an objective response rate of 60.6% (20/33), a median duration of response of 11.3 months, and a median progression free survival of 11.7 months in patients with advanced non-small cell lung cancer harboring a BRAF V600 mutation (Ann Oncol (2023) 34 (suppl_2): S790; NCT03781219). detail...
BRAF V600X skin melanoma sensitive Dabrafenib + Pembrolizumab + Trametinib Guideline Actionable Tafinlar (dabrafenib) plus Mekinist (trametinib) in combination with an immune checkpoint inhibitor, such as Keytruda (pembrolizumab), is included in guidelines as second-line or subsequent therapy (category 2A) for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 mutation (NCCN.org). detail...
BRAF V600X skin melanoma sensitive Atezolizumab + Cobimetinib + Vemurafenib Guideline Actionable Zelboraf (vemurafenib) plus Cotellic (cobimetinib) in combination with an immune checkpoint inhibitor, such as Tecentriq (atezolizumab), is included in guidelines as second-line or subsequent therapy (category 2A) for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 mutation (NCCN.org). detail...