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NM_000335.5(SCN5A):c.3953G>T (p.Gly1318Val) AND Cardiovascular phenotype

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Feb 22, 2024
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:
RCV000252945.12

Allele description [Variation Report for NM_000335.5(SCN5A):c.3953G>T (p.Gly1318Val)]

NM_000335.5(SCN5A):c.3953G>T (p.Gly1318Val)

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.3953G>T (p.Gly1318Val)
HGVS:
  • NC_000003.12:g.38562422C>A
  • NG_008934.1:g.92251G>T
  • NM_000335.5:c.3953G>TMANE SELECT
  • NM_001099404.2:c.3956G>T
  • NM_001099405.2:c.3956G>T
  • NM_001160160.2:c.3953G>T
  • NM_001160161.2:c.3794G>T
  • NM_001354701.2:c.3953G>T
  • NM_198056.3:c.3956G>T
  • NP_000326.2:p.Gly1318Val
  • NP_001092874.1:p.Gly1319Val
  • NP_001092875.1:p.Gly1319Val
  • NP_001153632.1:p.Gly1318Val
  • NP_001153633.1:p.Gly1265Val
  • NP_001341630.1:p.Gly1318Val
  • NP_932173.1:p.Gly1319Val
  • NP_932173.1:p.Gly1319Val
  • LRG_289t1:c.3956G>T
  • LRG_289:g.92251G>T
  • LRG_289p1:p.Gly1319Val
  • NC_000003.11:g.38603913C>A
  • NM_198056.2:c.3956G>T
  • Q14524:p.Gly1319Val
Protein change:
G1265V
Links:
UniProtKB: Q14524#VAR_026375; dbSNP: rs199473220
NCBI 1000 Genomes Browser:
rs199473220
Molecular consequence:
  • NM_000335.5:c.3953G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.3956G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.3956G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.3953G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.3794G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.3953G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.3956G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000319730Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Feb 22, 2024) 		germlineclinical testing

PubMed (14)
[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

Genotype-phenotype relationship in Brugada syndrome: electrocardiographic features differentiate SCN5A-related patients from non-SCN5A-related patients.

Smits JP, Eckardt L, Probst V, Bezzina CR, Schott JJ, Remme CA, Haverkamp W, Breithardt G, Escande D, Schulze-Bahr E, LeMarec H, Wilde AA.

J Am Coll Cardiol. 2002 Jul 17;40(2):350-6.

PubMed [citation]
PMID:
12106943

Characterization of a novel SCN5A mutation associated with Brugada syndrome reveals involvement of DIIIS4-S5 linker in slow inactivation.

Casini S, Tan HL, Bhuiyan ZA, Bezzina CR, Barnett P, Cerbai E, Mugelli A, Wilde AA, Veldkamp MW.

Cardiovasc Res. 2007 Dec 1;76(3):418-29. Epub 2007 Aug 22.

PubMed [citation]
PMID:
17854786
See all PubMed Citations (14)

Details of each submission

From Ambry Genetics, SCV000319730.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (14)

Description

The p.G1319V variant (also known as c.3956G>T), located in coding exon 21 of the SCN5A gene, results from a G to T substitution at nucleotide position 3956. The glycine at codon 1319 is replaced by valine, an amino acid with dissimilar properties. This variant has been previously reported in multiple affected individuals with confirmed or suspected Brugada syndrome or other arrhythmia phenotypes (Casini S et al. Cardiovasc Res. 2007;76(3):418-29; Meregalli PG et al. Heart Rhythm. 2009;6(3):341-8; Kapplinger JD et al. Heart Rhythm. 2010;7(1):33-46; van der Werf C et al. Heart Rhythm. 2010;7(10):1383-9; Amin AS et al. Europace. 2011;13(7):968-75), and was also reported in an adult male with dilated cardiomyopathy (DCM) and arrhythmia, and in his son who had signs of DCM (Golbus JR et al. Circ Cardiovasc Genet. 2014;7(6):751-9 (reported as p.G1318V)). One study reported that this alteration resulted in abnormal ion channel function (Casini S et al. Cardiovasc Res. 2007;76(3):418-29), while a second study found no impact on sodium current density when co-expressed with wild-type channels (Hoshi M et al. Circ Cardiovasc Genet. 2014;7(2):123-31). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: Nov 10, 2024