NM_004333.6(BRAF):c.1914T>G (p.Asp638Glu) AND not provided

Germline classification:: Pathogenic (5 submissions)
Last evaluated:: Dec 28, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000157831.36

Allele description [Variation Report for NM_004333.6(BRAF):c.1914T>G (p.Asp638Glu)]

NM_004333.6(BRAF):c.1914T>G (p.Asp638Glu)

Gene:

BRAF:B-Raf proto-oncogene, serine/threonine kinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q34

Genomic location:

Preferred name:

NM_004333.6(BRAF):c.1914T>G (p.Asp638Glu)

Other names:

p.D638E:GAT>GAG

HGVS:

NC_000007.14:g.140749365A>C
NG_007873.3:g.180400T>G
NM_001354609.2:c.1914T>G
NM_001374244.1:c.2034T>G
NM_001374258.1:c.2034T>G
NM_001378467.1:c.1923T>G
NM_001378468.1:c.1914T>G
NM_001378469.1:c.1848T>G
NM_001378470.1:c.1812T>G
NM_001378471.1:c.1803T>G
NM_001378472.1:c.1758T>G
NM_001378473.1:c.1758T>G
NM_001378474.1:c.1914T>G
NM_001378475.1:c.1650T>G
NM_004333.6:c.1914T>GMANE SELECT
NP_001341538.1:p.Asp638Glu
NP_001361173.1:p.Asp678Glu
NP_001361187.1:p.Asp678Glu
NP_001365396.1:p.Asp641Glu
NP_001365397.1:p.Asp638Glu
NP_001365398.1:p.Asp616Glu
NP_001365399.1:p.Asp604Glu
NP_001365400.1:p.Asp601Glu
NP_001365401.1:p.Asp586Glu
NP_001365402.1:p.Asp586Glu
NP_001365403.1:p.Asp638Glu
NP_001365404.1:p.Asp550Glu
NP_004324.2:p.Asp638Glu
LRG_299t1:c.1914T>G
LRG_299:g.180400T>G
NC_000007.13:g.140449165A>C
NM_004333.4:c.1914T>G
NM_004333.5:c.1914T>G
NM_004333.6:c.1914T>G
P15056:p.Asp638Glu

Protein change:

D550E

Links:

UniProtKB: P15056#VAR_058630; dbSNP: rs180177042

NCBI 1000 Genomes Browser:

rs180177042

Molecular consequence:

NM_001354609.2:c.1914T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374244.1:c.2034T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374258.1:c.2034T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378467.1:c.1923T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378468.1:c.1914T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378469.1:c.1848T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378470.1:c.1812T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378471.1:c.1803T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378472.1:c.1758T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378473.1:c.1758T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378474.1:c.1914T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378475.1:c.1650T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_004333.6:c.1914T>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000207761	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Dec 28, 2022)	germline	clinical testing	Citation Link,
SCV001247573	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Nov 1, 2020)	germline	clinical testing	Citation Link,
SCV001809483	Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001932077	Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001959358	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000207761.13

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; The majority of missense variants in this gene are considered pathogenic [(HGMD]; This variant is associated with the following publications: (PMID: 27171548, 30141192, 23093928, 25525159, 19206169, 18413255, 21063443, 30556322, 32369273, 33040082, 31069529, 34643321)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV001247573.30

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		2	not provided	not provided	not provided

From Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus, SCV001809483.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV001932077.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001959358.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 25, 2025

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