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NM_000335.5(SCN5A):c.5126C>T (p.Ser1709Leu) AND Cardiovascular phenotype

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jan 12, 2022
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:
RCV000246596.11

Allele description [Variation Report for NM_000335.5(SCN5A):c.5126C>T (p.Ser1709Leu)]

NM_000335.5(SCN5A):c.5126C>T (p.Ser1709Leu)

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.5126C>T (p.Ser1709Leu)
Other names:
p.S1710L:TCG>TTG; p.Ser1710Leu
HGVS:
  • NC_000003.12:g.38551243G>A
  • NG_008934.1:g.103430C>T
  • NM_000335.5:c.5126C>TMANE SELECT
  • NM_001099404.2:c.5129C>T
  • NM_001099405.2:c.5075C>T
  • NM_001160160.2:c.5030C>T
  • NM_001160161.2:c.4967C>T
  • NM_001354701.2:c.5072C>T
  • NM_198056.3:c.5129C>T
  • NP_000326.2:p.Ser1709Leu
  • NP_001092874.1:p.Ser1710Leu
  • NP_001092874.1:p.Ser1710Leu
  • NP_001092875.1:p.Ser1692Leu
  • NP_001153632.1:p.Ser1677Leu
  • NP_001153633.1:p.Ser1656Leu
  • NP_001341630.1:p.Ser1691Leu
  • NP_932173.1:p.Ser1710Leu
  • NP_932173.1:p.Ser1710Leu
  • LRG_289t1:c.5129C>T
  • LRG_289t3:c.5129C>T
  • LRG_289:g.103430C>T
  • LRG_289p1:p.Ser1710Leu
  • LRG_289p3:p.Ser1710Leu
  • NC_000003.11:g.38592734G>A
  • NM_001099404.1:c.5129C>T
  • NM_198056.2:c.5129C>T
Protein change:
S1656L; SER1710LEU
Links:
OMIM: 600163.0014; dbSNP: rs137854604
NCBI 1000 Genomes Browser:
rs137854604
Molecular consequence:
  • NM_000335.5:c.5126C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.5129C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.5075C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.5030C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.4967C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.5072C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.5129C>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
SCV000319116Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Jan 12, 2022) 		germlineclinical testing

PubMed (12)
[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

A novel SCN5A mutation associated with idiopathic ventricular fibrillation without typical ECG findings of Brugada syndrome.

Akai J, Makita N, Sakurada H, Shirai N, Ueda K, Kitabatake A, Nakazawa K, Kimura A, Hiraoka M.

FEBS Lett. 2000 Aug 11;479(1-2):29-34.

PubMed [citation]
PMID:
10940383

Sodium channel gene (SCN5A) mutations in 44 index patients with Brugada syndrome: different incidences in familial and sporadic disease.

Schulze-Bahr E, Eckardt L, Breithardt G, Seidl K, Wichter T, Wolpert C, Borggrefe M, Haverkamp W.

Hum Mutat. 2003 Jun;21(6):651-2. Erratum in: Hum Mutat. 2005 Jul;26(1):61.

PubMed [citation]
PMID:
14961552
See all PubMed Citations (12)

Details of each submission

From Ambry Genetics, SCV000319116.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (12)

Description

The p.S1710L variant (also known as c.5129C>T) is located in coding exon 27 of the SCN5A gene. This alteration results from a C to T substitution at nucleotide position 5129. The serine at codon 1710 is replaced by leucine, an amino acid with dissimilar properties. This variant has been reported in individuals with Brugada syndrome (Shin DJ et al. Life Sci, 2007 Jan;80:716-24; Millat G et al. Clin Biochem, 2009 Apr;42:491-9; Lee H et al. JAMA, 2014 Nov;312:1880-7; Ciconte G et al. Eur Heart J, 2021 03;42:1082-1090). This variant has also been detected in individuals with other SCN5A-related arrhythmias, including idiopathic ventricular fibrillation (IVF), progressive family heart block, and sick sinus syndrome (Akai J et al. FEBS Lett, 2000 Aug;479:29-34; Makita N et al. Circ Arrhythm Electrophysiol, 2012 Feb;5:163-72; Lee YS et al. Korean Circ J, 2016 Jan;46:63-71). Limited functional studies in human kidney cells have demonstrated that the alteration affected the duration of activation and inactivation of the protein (Akai J et al FEBS Lett. 2000;479(1-2):29-34 and Sharai N et al. Cardiovasc Res. 2002;53(2):348-354). 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: Jul 23, 2024