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NM_000335.4(SCN5A):c.1535C>T (p.Thr512Ile)

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Interpretation:
Uncertain significance​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
5 (Most recent: Aug 15, 2018)
Last evaluated:
Feb 17, 2017
Accession:
VCV000067665.2
Variation ID:
67665
Description:
single nucleotide variant
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NM_000335.4(SCN5A):c.1535C>T (p.Thr512Ile)

Allele ID
24437
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
3p22.2
Genomic location
3: 38604067 (GRCh38) GRCh38 UCSC
3: 38645558 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_289:g.50606C>T
Q14524:p.Thr512Ile
NC_000003.11:g.38645558G>A
... more HGVS
Protein change
T512I
Other names
-
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00000
Exome Aggregation Consortium (ExAC) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Links
UniProtKB: Q14524#VAR_036662
OMIM: 600163.0031
dbSNP: rs199473118
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 1 criteria provided, single submitter Mar 27, 2016 RCV000234724.1
Uncertain significance 2 criteria provided, single submitter Feb 17, 2017 RCV000588264.2
Pathogenic 1 no assertion criteria provided Apr 10, 2014 RCV000144029.2
not provided 1 no assertion provided - RCV000058426.3
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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 Some evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
1470 1628

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Mar 27, 2016)
criteria provided, single submitter
Method: clinical testing
Brugada syndrome
Allele origin: germline
Invitae
Accession: SCV000291778.2
Submitted: (Jun 10, 2016)
Evidence details
Comment:
This sequence change replaces threonine with isoleucine at codon 512 of the SCN5A protein (p.Thr512Ile). The threonine residue is moderately conserved and there is a ... (more)
Uncertain significance
(Feb 17, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Integrated Genetics/Laboratory Corporation of America
Accession: SCV000700018.1
Submitted: (Jan 25, 2018)
Evidence details
Publications
PubMed (2)
Comment:
Variant summary: The SCN5A c.1535C>T (p.Thr512Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. 2/3 in silico tools predict a benign ... (more)
Pathogenic
(Apr 10, 2014)
no assertion criteria provided
Method: literature only
Brugada Syndrome 1
Allele origin: germline
GeneReviews
Accession: SCV000188922.2
Submitted: (Sep 09, 2014)
Evidence details
Uncertain significance
(Apr 22, 2016)
no assertion criteria provided
Method: provider interpretation
not provided
Allele origin: germline
Stanford Center for Inherited Cardiovascular Disease,Stanford University
Accession: SCV000924956.1
Submitted: (Aug 15, 2018)
Evidence details
Comment:
The variant has been reported in one 2-year-old individual with second-degree atrioventricular (AV) block (Viswanathan 2003). Functional expression studies showed that voltage-dependent activation and inactivation ... (more)
not provided
(-)
no assertion provided
Method: literature only
Cardiac conduction defect, nonspecific
Allele origin: germline
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust
Accession: SCV000089946.3
Submitted: (Sep 22, 2016)
Evidence details
Publications
PubMed (2)
Comment:
This variant has been reported as associated with Cardiac conduction disease in the following publications (PMID:12569159). This is a literature report, and does not necessarily ... (more)

Citations for this variant

Title Author Journal Year Link
Analysis of SCN5A Gene Variants in East Slovak Patients with Cardiomyopathy. Priganc M Journal of clinical laboratory analysis 2017 PMID: 27554632
Brugada Syndrome Brugada R - 2016 PMID: 20301690
Paralogous annotation of disease-causing variants in long QT syndrome genes. Ware JS Human mutation 2012 PMID: 22581653
A common SCN5A polymorphism modulates the biophysical effects of an SCN5A mutation. Viswanathan PC The Journal of clinical investigation 2003 PMID: 12569159

Record last updated Oct 11, 2019