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NM_000335.5(SCN5A):c.2632C>T (p.Arg878Cys)

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Interpretation:
Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
4 (Most recent: Sep 25, 2021)
Last evaluated:
Jul 28, 2020
Accession:
VCV000067744.6
Variation ID:
67744
Description:
single nucleotide variant
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NM_000335.5(SCN5A):c.2632C>T (p.Arg878Cys)

Allele ID
78639
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
3p22.2
Genomic location
3: 38585846 (GRCh38) GRCh38 UCSC
3: 38627337 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_289:g.68827C>T
Q14524:p.Arg878Cys
NC_000003.11:g.38627337G>A
... more HGVS
Protein change
R878C
Other names
p.R878C:CGC>TGC
Canonical SPDI
NC_000003.12:38585845:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA016333
UniProtKB: Q14524#VAR_055183
dbSNP: rs199473168
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 2 criteria provided, single submitter Jul 8, 2020 RCV000058513.4
Likely pathogenic 1 criteria provided, single submitter Jul 28, 2020 RCV000183008.3
Likely pathogenic 1 criteria provided, single submitter Aug 9, 2018 RCV000621112.1
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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
Likely pathogenic
(Jul 28, 2020)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000235414.12
Submitted: (Sep 25, 2021)
Evidence details
Comment:
Reported to segregate with varying arrhythmia phenotypes in four individuals from one family (Zhang et al., 2008); Not observed in large population cohorts (Lek et … (more)
Likely pathogenic
(Aug 09, 2018)
criteria provided, single submitter
Method: clinical testing
Cardiovascular phenotype
Allele origin: germline
Ambry Genetics
Accession: SCV000737852.3
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (9)
Comment:
The p.R878C variant (also known as c.2632C>T), located in coding exon 15 of the SCN5A gene, results from a C to T substitution at nucleotide … (more)
Likely pathogenic
(Jul 08, 2020)
criteria provided, single submitter
Method: clinical testing
Brugada syndrome
Allele origin: germline
Invitae
Accession: SCV001214073.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (8)
Comment:
This sequence change replaces arginine with cysteine at codon 878 of the SCN5A protein (p.Arg878Cys). The arginine residue is highly conserved and there is a … (more)
not provided
(-)
no assertion provided
Method: literature only
Brugada syndrome
Allele origin: germline
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust
Accession: SCV000090033.3
Submitted: (Sep 22, 2016)
Evidence details
Publications
PubMed (5)
Comment:
This variant has been reported as associated with Brugada syndrome in the following publications (PMID:18616619;PMID:20129283;PMID:20539757;PMID:20960617). 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
Prolonged Right Ventricular Ejection Delay in Brugada Syndrome Depends on the Type of SCN5A Variant - Electromechanical Coupling Through Tissue Velocity Imaging as a Bridge Between Genotyping and Phenotyping. Van Malderen SCH Circulation journal : official journal of the Japanese Circulation Society 2017 PMID: 28781330
Utility of Post-Mortem Genetic Testing in Cases of Sudden Arrhythmic Death Syndrome. Lahrouchi N Journal of the American College of Cardiology 2017 PMID: 28449774
Genotype-Phenotype Correlation of <i>SCN5A</i> Mutation for the Clinical and Electrocardiographic Characteristics of Probands With Brugada Syndrome: A Japanese Multicenter Registry. Yamagata K Circulation 2017 PMID: 28341781
SCN4A variants and Brugada syndrome: phenotypic and genotypic overlap between cardiac and skeletal muscle sodium channelopathies. Bissay V European journal of human genetics : EJHG 2016 PMID: 26036855
A comprehensive electrocardiographic, molecular, and echocardiographic study of Brugada syndrome: validation of the 2013 diagnostic criteria. Savastano S Heart rhythm 2014 PMID: 24721456
Spectrum and prevalence of mutations involving BrS1- through BrS12-susceptibility genes in a cohort of unrelated patients referred for Brugada syndrome genetic testing: implications for genetic testing. Crotti L Journal of the American College of Cardiology 2012 PMID: 22840528
Dominant-negative effect of SCN5A N-terminal mutations through the interaction of Na(v)1.5 α-subunits. Clatot J Cardiovascular research 2012 PMID: 22739120
Paralogous annotation of disease-causing variants in long QT syndrome genes. Ware JS Human mutation 2012 PMID: 22581653
Multiple loss-of-function mechanisms contribute to SCN5A-related familial sick sinus syndrome. Gui J PloS one 2010 PMID: 20539757
Mutation-specific effects of polymorphism H558R in SCN5A-related sick sinus syndrome. Gui J Journal of cardiovascular electrophysiology 2010 PMID: 20384651
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
Gene symbol: SCN5A. Disease: Brugada syndrome. Crotti L Human genetics 2008 PMID: 20960618
Gene symbol: SCN5A. Disease: Brugada syndrome. Crotti L Human genetics 2008 PMID: 20960617
Correlations between clinical and physiological consequences of the novel mutation R878C in a highly conserved pore residue in the cardiac Na+ channel. Zhang Y Acta physiologica (Oxford, England) 2008 PMID: 18616619
Novel human pathological mutations. - Human genetics 2008 PMID: 18465145

Text-mined citations for rs199473168...

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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 Nov 27, 2021