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NM_000335.5(SCN5A):c.4744C>T (p.Arg1582Cys)

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Interpretation:
Uncertain significance​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
6 (Most recent: Jan 7, 2021)
Last evaluated:
May 31, 2020
Accession:
VCV000067920.8
Variation ID:
67920
Description:
single nucleotide variant
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NM_000335.5(SCN5A):c.4744C>T (p.Arg1582Cys)

Allele ID
78813
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
3p22.2
Genomic location
3: 38554345 (GRCh38) GRCh38 UCSC
3: 38595836 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
Q14524:p.Arg1583Cys
LRG_289t1:c.4747C>T LRG_289p1:p.Arg1583Cys
NC_000003.11:g.38595836G>A
... more HGVS
Protein change
R1582C, R1583C, R1529C, R1564C, R1565C
Other names
-
Canonical SPDI
NC_000003.12:38554344:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00001
Links
ClinGen: CA018516
UniProtKB: Q14524#VAR_074456
dbSNP: rs45514691
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, single submitter May 31, 2020 RCV000058701.5
Uncertain significance 1 criteria provided, single submitter Sep 11, 2018 RCV000154836.2
Uncertain significance 2 criteria provided, single submitter Feb 25, 2020 RCV000850283.2
Uncertain significance 1 criteria provided, single submitter Jan 22, 2020 RCV001289206.1
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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
(Sep 11, 2018)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000204518.5
Submitted: (Mar 21, 2019)
Evidence details
Publications
PubMed (2)
Comment:
proposed classification - variant undergoing re-assessment, contact laboratory
Uncertain significance
(May 31, 2020)
criteria provided, single submitter
Method: clinical testing
Brugada syndrome
Allele origin: germline
Invitae
Accession: SCV000545079.5
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (2)
Comment:
This sequence change replaces arginine with cysteine at codon 1583 of the SCN5A protein (p.Arg1583Cys). The arginine residue is highly conserved and there is a … (more)
Uncertain significance
(Feb 25, 2020)
criteria provided, single submitter
Method: clinical testing
Arrhythmia
Allele origin: germline
Color Health, Inc
Accession: SCV001350456.1
Submitted: (May 19, 2020)
Comment:
This missense variant replaces arginine with cysteine at codon 1583 of the SCN5A protein. Computational prediction suggests that this variant may have deleterious impact on … (more)
Evidence details
Uncertain significance
(Jan 22, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: unknown
Athena Diagnostics Inc
Accession: SCV001476865.1
Submitted: (Dec 30, 2020)
Evidence details
Publications
PubMed (5)
Likely pathogenic
(-)
no assertion criteria provided
Method: clinical testing
Arrhythmia
Allele origin: unknown
Institute of Human Genetics,University of Wuerzburg
Accession: SCV000992458.1
Submitted: (Sep 14, 2019)
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: SCV000090221.3
Submitted: (Sep 22, 2016)
Evidence details
Publications
PubMed (2)
Comment:
This variant has been reported as associated with Brugada syndrome in the following publications (PMID:20129283). 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
Impact of Ancestral Differences and Reassessment of the Classification of Previously Reported Pathogenic Variants in Patients With Brugada Syndrome in the Genomic Era: A SADS-TW BrS Registry. Chen CJ Frontiers in genetics 2019 PMID: 30662450
A multiplex PCR strategy to screen for known mutations in families with sudden cardiac death burden. Duong G Journal of biological methods 2017 PMID: 31453232
Testing the burden of rare variation in arrhythmia-susceptibility genes provides new insights into molecular diagnosis for Brugada syndrome. Le Scouarnec S Human molecular genetics 2015 PMID: 25650408
Paralogue annotation identifies novel pathogenic variants in patients with Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia. Walsh R Journal of medical genetics 2014 PMID: 24136861
Paralogous annotation of disease-causing variants in long QT syndrome genes. Ware JS Human mutation 2012 PMID: 22581653
An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing. Kapplinger JD Heart rhythm 2010 PMID: 20129283

Text-mined citations for rs45514691...

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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