Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation

ClinVar Genomic variation as it relates to human health

Advanced search

NM_001374258.1(BRAF):c.1621G>A (p.Glu541Lys)

Help
Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
5 (Most recent: Mar 28, 2019)
Last evaluated:
Dec 21, 2018
Accession:
VCV000013977.3
Variation ID:
13977
Description:
single nucleotide variant
Help

NM_001374258.1(BRAF):c.1621G>A (p.Glu541Lys)

Allele ID
29016
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
7q34
Genomic location
7: 140778007 (GRCh38) GRCh38 UCSC
7: 140477807 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000007.13:g.140477807C>T
NC_000007.14:g.140778007C>T
NM_001374258.1:c.1621G>A MANE Select NP_001361187.1:p.Glu541Lys missense
... more HGVS
Protein change
E501K, E504K, E541K, E467K, E413K, E449K, E464K, E479K
Other names
-
Canonical SPDI
NC_000007.14:140778006:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA273130
UniProtKB: P15056#VAR_026118
OMIM: 164757.0017
dbSNP: rs180177038
Varsome
Help

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic/Likely pathogenic 2 criteria provided, multiple submitters, no conflicts Dec 29, 2015 RCV000207513.2
Pathogenic 1 criteria provided, single submitter Dec 21, 2018 RCV000033315.4
Pathogenic 1 no assertion criteria provided Mar 1, 2006 RCV000015011.32
Pathogenic 1 no assertion criteria provided May 23, 2014 RCV000844616.1
Help
Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
BRAF Little evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
537 580

Submitted interpretations and evidence

Help
Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Jul 22, 2015)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: unknown
Molecular Diagnostics Lab,Nemours Alfred I. duPont Hospital for Children
Accession: SCV000263065.1
Submitted: (Dec 22, 2015)
Evidence details
Publications
PubMed (3)
Pathogenic
(Dec 29, 2015)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000338452.4
Submitted: (Sep 19, 2018)
Evidence details
Publications
PubMed (4)
Other databases
http://www.egl-eurofins.com/emvc…
Pathogenic
(Dec 21, 2018)
criteria provided, single submitter
Method: clinical testing
Rasopathy
Allele origin: germline
Invitae
Accession: SCV000948576.1
Submitted: (Mar 28, 2019)
Evidence details
Publications
PubMed (2)
Comment:
This sequence change replaces glutamic acid with lysine at codon 501 of the BRAF protein (p.Glu501Lys). The glutamic acid residue is highly conserved and there … (more)
Pathogenic
(Mar 01, 2006)
no assertion criteria provided
Method: literature only
CARDIOFACIOCUTANEOUS SYNDROME 1
Allele origin: germline
OMIM
Accession: SCV000035267.4
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (2)
Pathogenic
(May 23, 2014)
no assertion criteria provided
Method: clinical testing
Noonan syndrome
Cardio-facio-cutaneous syndrome
(Autosomal dominant inheritance)
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000197148.4
Submitted: (Mar 21, 2019)
Evidence details
Publications
PubMed (4)
Comment:
The Glu501Lys variant in BRAF has been previously identified in four patients wi th clinical features of the Noonan spectrum (Razzaque 2007, LMM unpublished data … (more)

Functional evidence

Help
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 this variant

Help
Title Author Journal Year Link
A structural systems biology approach for quantifying the systemic consequences of missense mutations in proteins. Cheng TM PLoS computational biology 2012 PMID: 23093928
Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: molecular diversity and associated phenotypic spectrum. Sarkozy A Human mutation 2009 PMID: 19206169
Germline gain-of-function mutations in RAF1 cause Noonan syndrome. Razzaque MA Nature genetics 2007 PMID: 17603482
Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome. Niihori T Nature genetics 2006 PMID: 16474404
Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome. Rodriguez-Viciana P Science (New York, N.Y.) 2006 PMID: 16439621
CFC syndrome: a syndrome distinct from Noonan syndrome. Verloes A Annales de genetique 1988 PMID: 3265306
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BRAF - - - -

Text-mined citations for rs180177038...

Help
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 07, 2021