Variant

BRAF V600

CI-VAR-00004571Explore in graph →p.Val600GluNM_004333.6:c.1799T>AClinVar 13961 CIViC 17 rs113488022

Curated evidence

Evidence by cancer (36 items)

Grouped by cancer context first, then therapy. The same variant can be sensitizing in one cancer and irrelevant in another — contexts are never merged. 50 items per page; a cancer group may continue on the next page.

civicCuratedShowing 1–36 of 36 evidence items across 10 cancer contexts on this page · levels, directions and significance as curated at the source; each row links to its CIViC record.

Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Childhood Low Grade Glioma2
BRAF V600	Dabrafenib	Predictive	B	Supports Sensitivity Response	3	submitted	EID8034 This clinical trial used a cohort of 32 pediatric low grade glioma (pLGG) patients. The primary endpoint of this study was objective response rate (ORR). In this study, an ORR of 44% and a 1-year prog… (full text at CIViC) PMID 31811016 · Hargrave et al., 2019 · Open in CIViC	civic
BRAF V600 OR v::BRAF Fusion	Tovorafenib	Predictive	A	Supports Sensitivity Response	5	accepted	EID12028 In this phase 2 clinical trial, the efficacy of RAF inhibitor tovorafenib (DAY-101) was investigated in patients between the ages of 6 months and 25 years, with pediatric low-grade gliomas harbouring … (full text at CIViC) PMID 37978284 · Kilburn et al., 2024 · Open in CIViC

ClinVar

Clinical significance (1)

ClinVar interpretations are shown as structured records — significance, review status, star rating, conditions — never flattened into one word.

clinvarCurated1 interpretation · review status and star rating as assigned by ClinVar.

Variation	Clinical significance	Review status	Stars	Conditions	Origin	Submitters	Last evaluated	Source
13961	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications	1	Carcinoma of colon; Papillary thyroid carcinoma; ASTROCYTOMA, LOW-GRADE, SOMATIC; Nongerminomatous germ cell tumor; Non-small cell lung carcinoma; Melanoma; Cardio-facio-cutaneous syndrome; Multiple myeloma; Neoplasm; Cystic epithelial invagination containing papillae lined by columnar epithelium; Cerebral arteriovenous malformation; Nephroblastoma; Malignant neoplastic disease; Colorectal cancer; Lymphangioma; Vascular malformation; Cardiovascular phenotype; Thyroid gland undifferentiated (anaplastic) carcinoma; Nodular ganglioneuroblastoma; Diffuse low-grade glioma, MAPK pathway–altered; Neuroblastoma; Diffuse midline glioma, H3 K27M-mutant; Malignant peripheral nerve sheath tumor; IDH-wildtype glioblastoma; Diffuse leptomeningeal glioneuronal tumor; Polymorphous low grade neuroepithelial tumor of the young; Benign metanephric tumor; Alveolar rhabdomyosarcoma; RASopathy; BRAF-related glioma susceptibility; Embryonal rhabdomyosarcoma; Spindle cell sarcoma; Dysembryoplastic neuroepithelial tumor; Pilocytic astrocytoma; Pleomorphic xanthoastrocytoma; Ganglioglioma; Malignant glioma

Cholangiocarcinoma1
BRAF V600	Vemurafenib	Predictive	B	Supports Sensitivity Response	4	accepted	EID5905 Eight patients with BRAF V600 (7 with V600E, 1 with V600 unknown) mutated cholangiocarcinoma received vemurafenib. Only one patients showed partial response and duration of response of this patient wa… (full text at CIViC) PMID 26287849 · Hyman et al., 2015 · Open in CIViC	civic

Cholangiocarcinoma1

BRAF V600

Vemurafenib

Predictive

Supports Sensitivity Response

accepted

EID5905

Eight patients with BRAF V600 (7 with V600E, 1 with V600 unknown) mutated cholangiocarcinoma received vemurafenib. Only one patients showed partial response and duration of response of this patient wa… (full text at CIViC)

PMID 26287849 · Hyman et al., 2015 · Open in CIViC

Malignant Colorectal Neoplasm8
BRAF V600	Cetuximab + VemurafenibCombination	Predictive	B	Does Not Support Sensitivity Response	2	accepted	EID1598 Patients with BRAF-V600 mutated cancers were identified (n=122) and subsequently underwent targeted therapy. 27 patients with colorectal cancer were treated with vemurafenib and cetuximab (N=24 with B… (full text at CIViC) PMID 26287849 · Hyman et al., 2015 · Open in CIViC	civic
BRAF V600	Dabrafenib + TrametinibCombination	Predictive	B	Supports Sensitivity Response	2	accepted	EID1415 In clinical trial NCT01072175, 43 patients with BRAF V600 metastatic colorectal cancer (CRC) received mutant BRAF inhibitor dabrafenib and MEK inhibitor trametinib. Only 12% of patients showed partia… (full text at CIViC) PMID 26392102 · Corcoran et al., 2015 · Open in CIViC	civic
BRAF V600	Dabrafenib + TrametinibCombination	Predictive	B	Does Not Support Sensitivity Response	2	rejected	EID1431 43 patients with BRAF V600 mutant colorectal cancer were treated with dabrafenib and trametinib. 24 patients had stable disease, 4 patients achieved partial response and one patient (not previously tr… (full text at CIViC) PMID 26392102 · Corcoran et al., 2015 · Open in CIViC	civic
BRAF V600	Cetuximab + EncorafenibCombination	Predictive	B	Supports Sensitivity Response	4	accepted	EID6046 In a Phase Ib Dose-Escalation Study of Encorafenib and Cetuximab, Twenty-six patients with refractory BRAF V600 mutant metastatic CRC (mCRC) were treated with a selective RAF kinase inhibitor (encoraf… (full text at CIViC) PMID 28363909 · van Geel et al., 2017 · Open in CIViC	civic
BRAF V600	Alpelisib + Cetuximab + EncorafenibCombination	Predictive	B	Supports Sensitivity Response	3	accepted	EID6047 In a phase Ib dose-escalation study of encorafenib, cetuximab and alpelisib, twenty-eight patients with refractory BRAF V600-mutant metastatic CRC (mCRC) were treated with a selective RAF kinase inhib… (full text at CIViC) PMID 28363909 · van Geel et al., 2017 · Open in CIViC	civic
BRAF V600	Panitumumab	Predictive	B	Supports Resistance	3	accepted	EID88 In metastatic colorectal cancer patients with wildtype KRAS, BRAF mutations were associated with poor progression free survival regardless of treatment (panitumumab with best supportive care or best s… (full text at CIViC) PMID 23325582 · Peeters et al., 2013 · Open in CIViC	civic
BRAF V600	Vemurafenib	Predictive	B	Supports Resistance	3	accepted	EID1576 Patients with BRAF-V600 mutated cancers were identified (n=122) and clinical response to vemurafenib was evaluated. Of the 10 patients with colorectal cancer (80% BRAF V600E, 20% V600 unknown status)… (full text at CIViC) PMID 26287849 · Hyman et al., 2015 · Open in CIViC	civic
BRAF V600	Cetuximab + Irinotecan + VemurafenibCombination	Predictive	B	Supports Sensitivity Response	3	accepted	EID7355 A randomized clinical trial was done with metastatic colorectal cancer (mCRC) patients (50 in the control group, 49 in the experimental group) with BRAF V600 mutations and RAS wild type that were enro… (full text at CIViC) Open in CIViC	civic

Melanoma18
BRAF V600	(diagnostic)	Diagnostic	B	Supports Positive	4	accepted	EID30 BRAF mutations are associated with melanoma arising in non-chronic sun damaged skin and with superficial spreading melanoma. PMID 21166657 · Lee et al., 2011 · Open in CIViC	civic
BRAF V600	Atezolizumab + Cobimetinib + VemurafenibCombination	Predictive	A	Supports Sensitivity Response	4	accepted	EID11238 In this phase 3, randomised, double-blind, placebo-controlled trial, 514 patients with unresectable stage IIIc–IV, BRAFV600 mutation-positive melanoma were randomly assigned to either 28-day cycles of… (full text at CIViC) PMID 32534646 · Gutzmer et al., 2020 · Open in CIViC	civic
BRAF V600	Atezolizumab + Cobimetinib + VemurafenibCombination	Predictive	A	Supports Sensitivity Response	4	submitted	EID13046 In the second interim analysis of the randomized phase III IMspire150 trial (NCT02908672), 514 patients with previously untreated unresectable stage IIIc or stage IV BRAF V600 mutation-positive melano… (full text at CIViC) PMID 36460017 · Ascierto et al., 2023 · Open in CIViC	civic
BRAF V600	Atezolizumab + Cobimetinib + VemurafenibCombination	Predictive	B	Supports Sensitivity Response	3	submitted	EID13043 In a multicenter, open-label phase Ib dose-escalation and cohort-expansion study (NCT01656642), 39 checkpoint inhibitor-naive patients with previously untreated, unresectable stage IIIC or metastatic … (full text at CIViC) PMID 31171876 · Sullivan et al., 2019 · Open in CIViC	civic
BRAF V600	Atezolizumab + Cobimetinib + VemurafenibCombination	Predictive	B	Supports Sensitivity Response	3	submitted	EID13044 In the multicenter, open-label, single-arm phase II TRICOTEL study (NCT03625141), 65 patients with previously untreated BRAF V600 mutation-positive metastatic melanoma and CNS metastases received vemu… (full text at CIViC) PMID 37459873 · Dummer et al., 2023 · Open in CIViC	civic
BRAF V600	Cobimetinib + VemurafenibCombination	Predictive	A	Supports Sensitivity Response	5	accepted	EID6044 In this double-blind, randomized, placebo-controlled, multicentre study, adult patients with histologically confirmed BRAF(V600) mutation-positive unresectable stage IIIC or stage IV melanoma were ran… (full text at CIViC) PMID 27480103 · Ascierto et al., 2016 · Open in CIViC	civic
BRAF V600	Dabrafenib	Predictive	B	Supports Sensitivity Response	4	accepted	EID1407 In the NCT00880321 trial using mutant BRAF inhibitor dabrafenib in solid tumors, 10 cases of melanoma brain metastases were assessed for dabrafenib response. In nine patients a decrease in size of met… (full text at CIViC) PMID 22608338 · Falchook et al., 2012 · Open in CIViC	civic
BRAF V600	Dabrafenib + TrametinibCombination	Predictive	B	Supports Sensitivity Response	5	accepted	EID6937 In this Phase III trial (NCT01584648 COMBI-d), 423 previously untreated patients with unresectable stage IIIC or IV BRAF V600E or V600K mutant melanoma received dabrafenib and trametinib or dabrafenib… (full text at CIViC) PMID 25265492 · Long et al., 2014 · Open in CIViC	civic
BRAF V600	Binimetinib + EncorafenibCombination	Predictive	A	Supports Sensitivity Response	5	accepted	EID7287 In a phase 3 trial, patients with melanoma with BRAF V600E or V600K mutation were randomly assigned to encorafenib plus binimetinib or vemurafenib or encorafenib. mPFS was 14·9 months (95% CI 11·0-18·… (full text at CIViC) PMID 29573941 · Dummer et al., 2018 · Open in CIViC	civic
BRAF V600	Binimetinib + EncorafenibCombination	Predictive	B	Supports Sensitivity Response	4	submitted	EID13042 In the multicenter, open-label phase Ib/II trial NCT01543698, 55 patients with BRAF V600-mutant metastatic melanoma who had not previously received a BRAF inhibitor were treated with encorafenib plus … (full text at CIViC) PMID 32669376 · Sullivan et al., 2020 · Open in CIViC	civic
BRAF V600	Binimetinib + EncorafenibCombination	Predictive	B	Supports Sensitivity Response	3	submitted	EID13184 In a multicenter, open-label phase Ib/II study, 55 BRAFi-naïve patients with BRAF-mutant melanoma, including 49 (89%) with BRAF V600E and 5 (9%) with BRAF V600K, received encorafenib plus binimetinib.… (full text at CIViC) PMID 32669376 · Sullivan et al., 2020 · Open in CIViC	civic
BRAF V600	Refametinib	Predictive	C	Supports Resistance	2	accepted	EID1000 Phase I trial of the mitogen-activated protein kinase 1/2 inhibitor BAY 86-9766. 2 of 2 patients with BRAF mutant melanoma had moderate progressive disease (despite receiving the highest doses adminis… (full text at CIViC) PMID 23434733 · Weekes et al., 2013 · Open in CIViC	civic
BRAF V600	Trametinib	Predictive	B	Supports Sensitivity Response	3	accepted	EID1750 Patients who had histologically confirmed, unresectable stage IIIC or IV cutaneous melanoma with a V600E or V600K BRAF mutation were eligible for the study. 322 eligible patients (281 with the V600E m… (full text at CIViC) PMID 22663011 · Flaherty et al., 2012 · Open in CIViC	civic
BRAF V600	Dabrafenib + TrametinibCombination	Predictive	B	Supports Sensitivity Response	5	accepted	EID6180 Combination Dabrafenib and Trametinib treatment was assessed for adjuvant treatment of stage III resected BRAF V600 mutant melanoma in the COMBI-AD trial NCT01682083. Patients were treated with combin… (full text at CIViC) PMID 28891408 · Long et al., 2017 · Open in CIViC	civic
BRAF V600	Cobimetinib + VemurafenibCombination	Predictive	B	Supports Sensitivity Response	4	accepted	EID1422 In a randomized phase 3 study, previously untreated advanced or metastatic BRAF V600 mutation-positive melanoma patients treated with combination vemurafenib and cobimetinib showed improved progressio… (full text at CIViC) PMID 25265494 · Larkin et al., 2014 · Open in CIViC	civic
BRAF V600	Cobimetinib + VemurafenibCombination	Predictive	B	Supports Sensitivity Response	3	accepted	EID6966 In this Phase 1b study, 129 patients with unresectable or metastatic melanoma were verified for BRAF V600 mutation using the cobas 4800 mutation test were selected who had progressed on vemurafenib (6… (full text at CIViC) PMID 25037139 · Ribas et al., 2014 · Open in CIViC	civic
BRAF V600 AND BRAF Amplification	Dabrafenib + TrametinibCombination	Predictive	C	Supports Resistance	4	accepted	EID7677 In a retrospective study, authors analyzed BRAF V600 mutated melanoma metastases derived from 10 patients treated with the combination of dabrafenib and trametinib for resistance mechanisms and geneti… (full text at CIViC) PMID 25452114 · Long et al., 2014 · Open in CIViC	civic
BRAF V600 AND PTEN Underexpression	Vemurafenib	Predictive	D	Supports Resistance	4	accepted	EID6271 An in vitro study of M229 (a human melanoma cell line) endogenously expressing wildtype PTEN and BRAF V600E (a known BRAF inhibitor sensitizing mutation) found that PTEN knockdown cells (achieved via … (full text at CIViC) PMID 24265155 · Shi et al., 2014 · Open in CIViC	civic