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

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 24, 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:
RCV001842356.11

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:
Cardiac arrhythmia
Synonyms:
Cardiac rhythm disease
Identifiers:
EFO: EFO_0004269; MONDO: MONDO:0007263; MedGen: C0003811; Human Phenotype Ontology: HP:0011675

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002053642Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Oct 24, 2023) 		germlineclinical testing

PubMed (15)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Aspergillus osteomyelitis of sternum after cardiac surgery.

Attah CA, Cerruti MM.

N Y State J Med. 1979 Aug;79(9):1420-1. No abstract available.

PubMed [citation]
PMID:
291807

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
See all PubMed Citations (15)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV002053642.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (15)

Description

This missense variant replaces glycine with valine at codon 1319 of the SCN5A protein. This variant is also known as p.Gly1318Val in the literature based on a different NM_000335 transcript. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). This variant is found within a highly conserved region of the transmembrane domain III. Rare nontruncating variants in this region have been shown to be significantly overrepresented in individuals with Brugada syndrome and long QT syndrome (PMID: 32893267). Functional studies have shown that this variant causes a significant reduction in sodium current (PMID: 17854786, 19251209). This variant has been reported in over ten unrelated individuals affected with Brugada syndrome (PMID: 12106943, 17854786, 19251209, 21273195, 24951569, 29759671, 30847666, 32893267, 36516610, 37061847, ClinVar SCV000291807.6), in an individual affected with long QT syndrome (PMID: 32893267), and in two individuals affected with progressive cardiac conduction disorders (PMID: 30059973). This variant has been shown to segregates with disease in four first-degree relatives from two families affected with cardiac conduction disease and cardiomypoathy (PMID: 25179549, 28790152). This variant has been identified in 11/269654 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic.

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

Last Updated: Oct 8, 2024