ClinVar Genomic variation as it relates to human health
NM_004333.6(BRAF):c.1798_1799delinsAA (p.Val600Lys)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic(1); Uncertain significance(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_004333.6(BRAF):c.1798_1799delinsAA (p.Val600Lys)
Variation ID: 375941 Accession: VCV000375941.6
- Type and length
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Indel, 2 bp
- Location
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Cytogenetic: 7q34 7: 140753336-140753337 (GRCh38) [ NCBI UCSC ] 7: 140453136-140453137 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Mar 8, 2017 Apr 13, 2021 Jul 14, 2015 - HGVS
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Nucleotide Protein Molecular
consequenceNM_004333.6:c.1798_1799delinsAA MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004324.2:p.Val600Lys missense NM_001374258.1:c.1918_1919delinsAA MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001361187.1:p.Val640Lys missense NM_001354609.2:c.1798_1799delinsAA NP_001341538.1:p.Val600Lys missense NM_001374244.1:c.1918_1919delinsAA NP_001361173.1:p.Val640Lys missense NM_001378467.1:c.1807_1808delinsAA NP_001365396.1:p.Val603Lys missense NM_001378468.1:c.1798_1799delinsAA NP_001365397.1:p.Val600Lys missense NM_001378469.1:c.1732_1733delinsAA NP_001365398.1:p.Val578Lys missense NM_001378470.1:c.1696_1697delinsAA NP_001365399.1:p.Val566Lys missense NM_001378471.1:c.1687_1688delinsAA NP_001365400.1:p.Val563Lys missense NM_001378472.1:c.1642_1643delinsAA NP_001365401.1:p.Val548Lys missense NM_001378473.1:c.1642_1643delinsAA NP_001365402.1:p.Val548Lys missense NM_001378474.1:c.1798_1799delinsAA NP_001365403.1:p.Val600Lys missense NM_001378475.1:c.1534_1535delinsAA NP_001365404.1:p.Val512Lys missense NC_000007.14:g.140753336_140753337delinsTT NC_000007.13:g.140453136_140453137delinsTT NG_007873.3:g.176428_176429delinsAA LRG_299:g.176428_176429delinsAA LRG_299t1:c.1798_1799delinsAA - Protein change
- V600K, V512K, V548K, V563K, V566K, V578K, V603K, V640K
- Other names
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- Canonical SPDI
- NC_000007.14:140753335:AC:TT
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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BRAF | Little evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1224 | 1333 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (1) |
no assertion criteria provided
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Jul 14, 2015 | RCV000422502.1 | |
Uncertain significance (1) |
no assertion criteria provided
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- | RCV001355295.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Jul 14, 2015)
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no assertion criteria provided
Method: literature only
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Melanoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000504266.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001550139.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Number of individuals with the variant: 5
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Database of genomic biomarkers for cancer drugs and clinical targetability in solid tumors. | Dienstmann R | Cancer discovery | 2015 | PMID: 25656898 |
Prospective enterprise-level molecular genotyping of a cohort of cancer patients. | MacConaill LE | The Journal of molecular diagnostics : JMD | 2014 | PMID: 25157968 |
Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study. | McArthur GA | The Lancet. Oncology | 2014 | PMID: 24508103 |
Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma. | Ascierto PA | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2013 | PMID: 23918947 |
Clinical responses to selumetinib (AZD6244; ARRY-142886)-based combination therapy stratified by gene mutations in patients with metastatic melanoma. | Patel SP | Cancer | 2013 | PMID: 22972589 |
Activity of the oral MEK inhibitor trametinib in patients with advanced melanoma: a phase 1 dose-escalation trial. | Falchook GS | The Lancet. Oncology | 2012 | PMID: 22805292 |
Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. | Hauschild A | Lancet (London, England) | 2012 | PMID: 22735384 |
Improved survival with MEK inhibition in BRAF-mutated melanoma. | Flaherty KT | The New England journal of medicine | 2012 | PMID: 22663011 |
Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial. | Falchook GS | Lancet (London, England) | 2012 | PMID: 22608338 |
Routine multiplex mutational profiling of melanomas enables enrollment in genotype-driven therapeutic trials. | Lovly CM | PloS one | 2012 | PMID: 22536370 |
Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. | Sosman JA | The New England journal of medicine | 2012 | PMID: 22356324 |
Phase II, open-label, randomized trial of the MEK1/2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma. | Kirkwood JM | Clinical cancer research : an official journal of the American Association for Cancer Research | 2012 | PMID: 22048237 |
Improved survival with vemurafenib in melanoma with BRAF V600E mutation. | Chapman PB | The New England journal of medicine | 2011 | PMID: 21639808 |
Inhibition of mutated, activated BRAF in metastatic melanoma. | Flaherty KT | The New England journal of medicine | 2010 | PMID: 20818844 |
Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032. | Rubinstein JC | Journal of translational medicine | 2010 | PMID: 20630094 |
Determinants of BRAF mutations in primary melanomas. | Maldonado JL | Journal of the National Cancer Institute | 2003 | PMID: 14679157 |
Mutations of the BRAF gene in human cancer. | Davies H | Nature | 2002 | PMID: 12068308 |
http://docm.genome.wustl.edu/variants/ENST00000288602:c.1798GT>AA | - | - | - | - |
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Text-mined citations for rs121913227 ...
HelpRecord last updated Apr 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.