U.S. flag

An official website of the United States government

NM_000335.5(SCN5A):c.1425A>C (p.Arg475Ser) AND Cardiovascular phenotype

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 27, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002390208.9

Allele description [Variation Report for NM_000335.5(SCN5A):c.1425A>C (p.Arg475Ser)]

NM_000335.5(SCN5A):c.1425A>C (p.Arg475Ser)

Gene:
SCN5A:sodium voltage-gated channel alpha subunit 5 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p22.2
Genomic location:
Preferred name:
NM_000335.5(SCN5A):c.1425A>C (p.Arg475Ser)
HGVS:
  • NC_000003.12:g.38604822T>G
  • NG_008934.1:g.49851A>C
  • NM_000335.5:c.1425A>CMANE SELECT
  • NM_001099404.2:c.1425A>C
  • NM_001099405.2:c.1425A>C
  • NM_001160160.2:c.1425A>C
  • NM_001160161.2:c.1425A>C
  • NM_001354701.2:c.1425A>C
  • NM_198056.3:c.1425A>C
  • NP_000326.2:p.Arg475Ser
  • NP_001092874.1:p.Arg475Ser
  • NP_001092875.1:p.Arg475Ser
  • NP_001153632.1:p.Arg475Ser
  • NP_001153633.1:p.Arg475Ser
  • NP_001341630.1:p.Arg475Ser
  • NP_932173.1:p.Arg475Ser
  • NP_932173.1:p.Arg475Ser
  • LRG_289t1:c.1425A>C
  • LRG_289:g.49851A>C
  • LRG_289p1:p.Arg475Ser
  • NC_000003.11:g.38646313T>G
  • NM_198056.2:c.1425A>C
  • Q14524:p.Arg475Ser
Protein change:
R475S
Links:
UniProtKB: Q14524#VAR_074356; dbSNP: rs199473116
NCBI 1000 Genomes Browser:
rs199473116
Molecular consequence:
  • NM_000335.5:c.1425A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.1425A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.1425A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.1425A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.1425A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.1425A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.1425A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002698664Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Dec 27, 2023) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Spectrum and prevalence of cardiac sodium channel variants among black, white, Asian, and Hispanic individuals: implications for arrhythmogenic susceptibility and Brugada/long QT syndrome genetic testing.

Ackerman MJ, Splawski I, Makielski JC, Tester DJ, Will ML, Timothy KW, Keating MT, Jones G, Chadha M, Burrow CR, Stephens JC, Xu C, Judson R, Curran ME.

Heart Rhythm. 2004 Nov;1(5):600-7.

PubMed [citation]
PMID:
15851227

An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing.

Kapplinger JD, Tester DJ, Alders M, Benito B, Berthet M, Brugada J, Brugada P, Fressart V, Guerchicoff A, Harris-Kerr C, Kamakura S, Kyndt F, Koopmann TT, Miyamoto Y, Pfeiffer R, Pollevick GD, Probst V, Zumhagen S, Vatta M, Towbin JA, Shimizu W, Schulze-Bahr E, et al.

Heart Rhythm. 2010 Jan;7(1):33-46. doi: 10.1016/j.hrthm.2009.09.069. Epub 2009 Oct 8.

PubMed [citation]
PMID:
20129283
PMCID:
PMC2822446
See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV002698664.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

The p.R475S variant (also known as c.1425A>C), located in coding exon 10 of the SCN5A gene, results from an A to C substitution at nucleotide position 1425. The arginine at codon 475 is replaced by serine, an amino acid with dissimilar properties. This variant has been detected in a cohort of individuals with pacemakers (Celestino-Soper PB et al. PLoS One. 2016 Jan;11(1):e0147455); however, detail was limited. This variant has also been detected in ostensibly healthy cohorts (Ackerman MJ et al. Heart Rhythm, 2004 Nov;1:600-7; Kapplinger JD et al. Heart Rhythm, 2010 Jan;7:33-46). This alteration has also been reported in a sudden death cohort and a pediatric dilated cardiomyopathy (DCM) cohort (Salfati EL et al. Genome Med, 2019 Dec;11:83; Khan RS et al. J Am Heart Assoc, 2022 Jan;11:e022854). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 22, 2025