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NM_000335.5(SCN5A):c.880G>A (p.Val294Met)

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Interpretation:
Uncertain significance​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
8 (Most recent: Aug 20, 2021)
Last evaluated:
Apr 1, 2021
Accession:
VCV000068054.14
Variation ID:
68054
Description:
single nucleotide variant
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NM_000335.5(SCN5A):c.880G>A (p.Val294Met)

Allele ID
78945
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
3p22.2
Genomic location
3: 38609788 (GRCh38) GRCh38 UCSC
3: 38651279 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
Q14524:p.Val294Met
NC_000003.12:g.38609788C>T
NG_008934.1:g.44885G>A
... more HGVS
Protein change
V294M
Other names
-
Canonical SPDI
NC_000003.12:38609787:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00003
The Genome Aggregation Database (gnomAD) 0.00004
The Genome Aggregation Database (gnomAD) 0.00006
Trans-Omics for Precision Medicine (TOPMed) 0.00002
Exome Aggregation Consortium (ExAC) 0.00003
Links
ClinGen: CA019903
UniProtKB: Q14524#VAR_026349
dbSNP: rs199473086
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 2 criteria provided, multiple submitters, no conflicts Apr 1, 2021 RCV000998027.4
Uncertain significance 2 criteria provided, single submitter Sep 20, 2020 RCV000058857.5
Uncertain significance 1 criteria provided, single submitter Oct 20, 2016 RCV000455194.1
Uncertain significance 1 criteria provided, single submitter Apr 25, 2018 RCV000678952.1
Uncertain significance 1 criteria provided, single submitter Oct 31, 2018 RCV000765741.1
Uncertain significance 1 criteria provided, single submitter May 14, 2019 RCV000777706.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
SCN5A Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
2366 2620

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Oct 20, 2016)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000540292.1
Submitted: (Apr 03, 2017)
Evidence details
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more)
Uncertain significance
(Apr 25, 2018)
criteria provided, single submitter
Method: clinical testing
Long QT syndrome 3
Allele origin: unknown
Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues
Accession: SCV000805167.1
Submitted: (Jul 02, 2018)
Evidence details
Uncertain significance
(Oct 31, 2018)
criteria provided, single submitter
Method: clinical testing
Progressive familial heart block, type 1A
SUDDEN INFANT DEATH SYNDROME
Brugada syndrome 1
Dilated cardiomyopathy 1E
Paroxysmal familial ventricular fibrillation 1
Long QT syndrome 3
Sick sinus syndrome 1, autosomal recessive
Atrial fibrillation, familial, 10
Allele origin: unknown
Fulgent Genetics,Fulgent Genetics
Accession: SCV000897109.1
Submitted: (Nov 14, 2018)
Evidence details
Publications
PubMed (1)
DOI: 10.1038/gim.2015.30
Uncertain significance
(May 14, 2019)
criteria provided, single submitter
Method: clinical testing
Arrhythmia
Allele origin: germline
Color Health, Inc
Accession: SCV000913649.2
Submitted: (May 19, 2020)
Comment:
This missense variant replaces valine with methionine at codon 294 of the SCN5A protein. Computational prediction tools and conservation analyses suggest that this variant may … (more)
Evidence details
Uncertain significance
(Sep 20, 2020)
criteria provided, single submitter
Method: clinical testing
Brugada syndrome
Allele origin: germline
Invitae
Accession: SCV000760271.4
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (3)
Comment:
This sequence change replaces valine with methionine at codon 294 of the SCN5A protein (p.Val294Met). The valine residue is moderately conserved and there is a … (more)
Uncertain significance
(Apr 01, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001804355.1
Submitted: (Aug 20, 2021)
Evidence details
Comment:
Reported in association with arrhythmia (Priori et al., 2000; Marschall et al., 2019); however, detailed clinical information was not provided; Reported in ClinVar as a … (more)
Uncertain significance
(Apr 01, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
CeGaT Praxis fuer Humangenetik Tuebingen
Accession: SCV001153885.7
Submitted: (Jul 04, 2021)
Evidence details
not provided
(-)
no assertion provided
Method: literature only
Brugada syndrome
Allele origin: germline
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust
Accession: SCV000090377.3
Submitted: (Sep 22, 2016)
Evidence details
Publications
PubMed (3)
Comment:
This variant has been reported as associated with Brugada syndrome in the following publications (PMID:11901046;PMID:11076825). This is a literature report, and does not necessarily reflect … (more)

Functional evidence

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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

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Title Author Journal Year Link
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Richards S Genetics in medicine : official journal of the American College of Medical Genetics 2015 PMID: 25741868
Paralogous annotation of disease-causing variants in long QT syndrome genes. Ware JS Human mutation 2012 PMID: 22581653
A novel strategy using cardiac sodium channel polymorphic fragments to rescue trafficking-deficient SCN5A mutations. Shinlapawittayatorn K Circulation. Cardiovascular genetics 2011 PMID: 21840964
Natural history of Brugada syndrome: insights for risk stratification and management. Priori SG Circulation 2002 PMID: 11901046
Clinical and genetic heterogeneity of right bundle branch block and ST-segment elevation syndrome: A prospective evaluation of 52 families. Priori SG Circulation 2000 PMID: 11076825

Text-mined citations for rs199473086...

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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 Dec 04, 2021