VCV000044803.4 - ClinVar

NM_004333.6(BRAF):c.1406G>T (p.Gly469Val)

Germline

Classification

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.

(10)

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

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_004333.6(BRAF):c.1406G>T (p.Gly469Val)

Variation ID: 44803 Accession: VCV000044803.4

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7q34 7: 140781602 (GRCh38) [ NCBI UCSC ] 7: 140481402 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	Jan 31, 2015	Mar 8, 2017	Dec 30, 2011

HGVS

Nucleotide	Protein	Molecular consequence
NM_004333.6:c.1406G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_004324.2:p.Gly469Val	missense
NM_001374258.1:c.1526G>T MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001361187.1:p.Gly509Val	missense
NM_001354609.2:c.1406G>T	NP_001341538.1:p.Gly469Val	missense
NM_001374244.1:c.1526G>T	NP_001361173.1:p.Gly509Val	missense
NM_001378467.1:c.1415G>T	NP_001365396.1:p.Gly472Val	missense
NM_001378468.1:c.1406G>T	NP_001365397.1:p.Gly469Val	missense
NM_001378469.1:c.1340G>T	NP_001365398.1:p.Gly447Val	missense
NM_001378470.1:c.1304G>T	NP_001365399.1:p.Gly435Val	missense
NM_001378471.1:c.1295G>T	NP_001365400.1:p.Gly432Val	missense
NM_001378472.1:c.1250G>T	NP_001365401.1:p.Gly417Val	missense
NM_001378473.1:c.1250G>T	NP_001365402.1:p.Gly417Val	missense
NM_001378474.1:c.1406G>T	NP_001365403.1:p.Gly469Val	missense
NM_001378475.1:c.1142G>T	NP_001365404.1:p.Gly381Val	missense
NC_000007.14:g.140781602C>A
NC_000007.13:g.140481402C>A
NG_007873.3:g.148163G>T
LRG_299:g.148163G>T
LRG_299t1:c.1406G>T
	P15056:p.Gly469Val

... more HGVS ... less HGVS

Protein change

G469V, G381V, G435V, G447V, G417V, G432V, G472V, G509V

Other names

Canonical SPDI

NC_000007.14:140781601:C:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

UniProtKB: P15056#VAR_040392 dbSNP: rs121913355 ClinGen: CA135085 VarSome

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
Gene	OMIM	HI score Help 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.
BRAF		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	1250	1364

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 Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Non-small cell lung carcinoma	Pathogenic (1)	criteria provided, single submitter	Dec 30, 2011	RCV000037919.5
Prostate adenocarcinoma	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000425868.1
Squamous cell carcinoma of the skin	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000436583.1
Multiple myeloma	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000418480.1
Lung adenocarcinoma	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000427987.1
Neoplasm of the large intestine	Pathogenic (1)	no assertion criteria provided	Oct 2, 2014	RCV000420102.1
Squamous cell lung carcinoma	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000445054.1
Neoplasm	Likely pathogenic (1)	no assertion criteria provided	Jul 14, 2015	RCV000430773.1
Transitional cell carcinoma of the bladder	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000435417.1
Malignant melanoma of skin	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000436805.1

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.
Pathogenic (Dec 30, 2011)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	Non-small cell lung carcinoma Affected status: not provided Allele origin: somatic	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000061582.4 First in ClinVar: May 03, 2013 Last updated: Jan 31, 2015	Publications: PubMed (1) PubMed: 12068308 Number of individuals with the variant: 2
Pathogenic (Oct 02, 2014)	no assertion criteria provided Method: literature only	Neoplasm of the large intestine (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000504323.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (6) PubMed: 22310681‚ 12068308‚ 20350999‚ 21129611‚ 18186519‚ 19537845 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000496384:c.230G>T
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	Malignant melanoma of skin (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000505817.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000288602:c.1406G>T
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	Squamous cell lung carcinoma (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000505818.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000288602:c.1406G>T
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	Prostate adenocarcinoma (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000505819.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000288602:c.1406G>T
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	Multiple myeloma (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000505821.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000288602:c.1406G>T
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	Transitional cell carcinoma of the bladder (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000505823.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000288602:c.1406G>T
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	None (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000505825.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000288602:c.1406G>T
Likely pathogenic (Jul 14, 2015)	no assertion criteria provided Method: literature only	Neoplasm (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000504324.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 25157968 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000496384:c.230G>T
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	Squamous cell carcinoma of the skin (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000505820.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000288602:c.1406G>T

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

Title	Author	Journal	Year	Link
Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.	Chang MT	Nature biotechnology	2016	PMID: 26619011
Prospective enterprise-level molecular genotyping of a cohort of cancer patients.	MacConaill LE	The Journal of molecular diagnostics : JMD	2014	PMID: 25157968
The road to resistance: EGFR mutation and cetuximab.	Bardelli A	Nature medicine	2012	PMID: 22310681
Prognostic vs predictive molecular biomarkers in colorectal cancer: is KRAS and BRAF wild type status required for anti-EGFR therapy?	Rizzo S	Cancer treatment reviews	2010	PMID: 21129611
Prognostic and predictive biomarkers in resected colon cancer: current status and future perspectives for integrating genomics into biomarker discovery.	Tejpar S	The oncologist	2010	PMID: 20350999
Clinical biomarkers in oncology: focus on colorectal cancer.	De Roock W	Molecular diagnosis & therapy	2009	PMID: 19537845
Rapid identification of somatic mutations in colorectal and breast cancer tissues using mismatch repair detection (MRD).	Bentivegna S	Human mutation	2008	PMID: 18186519
Mutations of the BRAF gene in human cancer.	Davies H	Nature	2002	PMID: 12068308
http://docm.genome.wustl.edu/variants/ENST00000288602:c.1406G>T	-	-	-	-
http://docm.genome.wustl.edu/variants/ENST00000496384:c.230G>T	-	-	-	-

Text-mined citations for rs121913355 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jul 17, 2023

ClinVar Genomic variation as it relates to human health

NM_004333.6(BRAF):c.1406G>T (p.Gly469Val)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs121913355 ...