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NM_000335.5(SCN5A):c.4490T>C (p.Met1497Thr)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(2);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
4 (Most recent: Jan 7, 2021)
Last evaluated:
Jun 10, 2019
Accession:
VCV000067902.5
Variation ID:
67902
Description:
single nucleotide variant
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NM_000335.5(SCN5A):c.4490T>C (p.Met1497Thr)

Allele ID
78795
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
3p22.2
Genomic location
3: 38555705 (GRCh38) GRCh38 UCSC
3: 38597196 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_289:g.98968T>C
Q14524:p.Met1498Thr
NC_000003.11:g.38597196A>G
... more HGVS
Protein change
M1497T, M1498T, M1480T, M1444T, M1479T
Other names
p.M1498T:ATG>ACG
Canonical SPDI
NC_000003.12:38555704:A:G
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA018346
UniProtKB: Q14524#VAR_074744
dbSNP: rs199473263
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 1 criteria provided, single submitter Mar 7, 2017 RCV000183196.2
Uncertain significance 1 criteria provided, single submitter May 3, 2019 RCV000548196.4
Likely pathogenic 1 criteria provided, single submitter Jun 10, 2019 RCV000619022.1
not provided 1 no assertion provided - RCV000058682.3
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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
Likely pathogenic
(Mar 07, 2017)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000235614.12
Submitted: (Nov 28, 2017)
Evidence details
Comment:
The M1498T likely pathogenic variant in the SCN5A gene has been reported previously in association with LQTS, however no additional clinical or segregation information was … (more)
Likely pathogenic
(Jun 10, 2019)
criteria provided, single submitter
Method: clinical testing
Cardiovascular phenotype
Allele origin: germline
Ambry Genetics
Accession: SCV000737387.3
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (3)
Comment:
The p.M1498T variant (also known as c.4493T>C), located in coding exon 25 of the SCN5A gene, results from a T to C substitution at nucleotide … (more)
Uncertain significance
(May 03, 2019)
criteria provided, single submitter
Method: clinical testing
Brugada syndrome
Allele origin: germline
Invitae
Accession: SCV000637156.4
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (2)
Comment:
This sequence change replaces methionine with threonine at codon 1498 of the SCN5A protein (p.Met1498Thr). The methionine residue is highly conserved and there is a … (more)
not provided
(-)
no assertion provided
Method: literature only
Congenital long QT syndrome
Allele origin: germline
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust
Accession: SCV000090202.3
Submitted: (Sep 22, 2016)
Evidence details
Publications
PubMed (2)
Comment:
This variant has been reported as associated with Long QT syndrome in the following publications (PMID:16414944). This is a literature report, and does not necessarily … (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
Genetic analysis of cardiac SCN5A Gene in Iranian patients with hereditary cardiac arrhythmias. Asadi M Anatolian journal of cardiology 2016 PMID: 26467377
UniProt: a hub for protein information. UniProt Consortium. Nucleic acids research 2015 PMID: 25348405
Paralogous annotation of disease-causing variants in long QT syndrome genes. Ware JS Human mutation 2012 PMID: 22581653
Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Kapplinger JD Heart rhythm 2009 PMID: 19716085
Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice. Napolitano C JAMA 2005 PMID: 16414944

Text-mined citations for rs199473263...

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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