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NM_000335.5(SCN5A):c.3389C>T (p.Thr1130Ile)

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Interpretation:
Uncertain significance​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
5 (Most recent: Sep 30, 2021)
Last evaluated:
Jun 30, 2020
Accession:
VCV000067795.5
Variation ID:
67795
Description:
single nucleotide variant
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NM_000335.5(SCN5A):c.3389C>T (p.Thr1130Ile)

Allele ID
78690
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
3p22.2
Genomic location
3: 38576780 (GRCh38) GRCh38 UCSC
3: 38618271 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
Q14524:p.Thr1131Ile
NC_000003.11:g.38618271G>A
NC_000003.12:g.38576780G>A
... more HGVS
Protein change
T1130I, T1131I, T1077I
Other names
p.T1131I:ACC>ATC
Canonical SPDI
NC_000003.12:38576779:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00003
Exome Aggregation Consortium (ExAC) 0.00004
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
Trans-Omics for Precision Medicine (TOPMed) 0.00010
Links
ClinGen: CA017114
UniProtKB: Q14524#VAR_055186
dbSNP: rs199473197
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 Jul 25, 2019 RCV000587127.2
Uncertain significance 1 criteria provided, single submitter Jun 30, 2020 RCV000468996.3
Uncertain significance 1 criteria provided, single submitter Apr 30, 2019 RCV001189178.1
not provided 1 no assertion provided - RCV000058569.3
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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
2348 2600

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Jul 02, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000700032.1
Submitted: (Jan 25, 2018)
Evidence details
Publications
PubMed (4)
Comment:
Variant summary: The c.3392C>T (p.Thr1131Ile) in SCN5A gene is a missense change that involves a non-conserved nucleotide resulting in a non-conservative amino acid substitution located … (more)
Uncertain significance
(Jun 30, 2020)
criteria provided, single submitter
Method: clinical testing
Brugada syndrome
Allele origin: germline
Invitae
Accession: SCV000545083.4
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (2)
Comment:
This sequence change replaces threonine with isoleucine at codon 1131 of the SCN5A protein (p.Thr1131Ile). The threonine residue is weakly conserved and there is a … (more)
Uncertain significance
(Jul 25, 2019)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000235441.11
Submitted: (Sep 30, 2021)
Evidence details
Comment:
Identified in individuals referred for cardiac genetic testing at GeneDx; however, at least one of these probands harbored a pathogenic variant in another cardiac disease-related … (more)
Uncertain significance
(Apr 30, 2019)
criteria provided, single submitter
Method: clinical testing
Arrhythmia
Allele origin: germline
Color Health, Inc
Accession: SCV001356413.1
Submitted: (May 19, 2020)
Comment:
This missense variant replaces threonine with isoleucine at codon 1131 of the SCN5A protein. Computational prediction tools and conservation analyses suggest that this variant may … (more)
Evidence details
not provided
(-)
no assertion provided
Method: literature only
Atrial fibrillation
Allele origin: germline
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust
Accession: SCV000090089.3
Submitted: (Sep 22, 2016)
Evidence details
Publications
PubMed (2)
Comment:
This variant has been reported as associated with Atrial fibrillation in the following publications (PMID:18378609). 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
Enhanced Classification of Brugada Syndrome-Associated and Long-QT Syndrome-Associated Genetic Variants in the SCN5A-Encoded Na(v)1.5 Cardiac Sodium Channel. Kapplinger JD Circulation. Cardiovascular genetics 2015 PMID: 25904541
Cardiac channelopathy testing in 274 ethnically diverse sudden unexplained deaths. Wang D Forensic science international 2014 PMID: 24631775
Paralogous annotation of disease-causing variants in long QT syndrome genes. Ware JS Human mutation 2012 PMID: 22581653
Voltage-gated sodium channels: mutations, channelopathies and targets. Andavan GS Current medicinal chemistry 2011 PMID: 21143119
Cardiac sodium channel (SCN5A) variants associated with atrial fibrillation. Darbar D Circulation 2008 PMID: 18378609

Text-mined citations for rs199473197...

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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 Oct 24, 2021