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

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Dec 3, 2019
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:
RCV004017232.1

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:
Brugada syndrome
Synonyms:
Sudden unexpected nocturnal death syndrome; Sudden unexplained nocturnal death syndrome; Sudden Unexplained Death Syndrome; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015263; MedGen: C1142166; OMIM: PS601144

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004847789Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely Pathogenic
(Dec 3, 2019) 		germlineclinical testing

PubMed (10)
[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

A mutant cardiac sodium channel with multiple biophysical defects associated with overlapping clinical features of Brugada syndrome and cardiac conduction disease.

Shirai N, Makita N, Sasaki K, Yokoi H, Sakuma I, Sakurada H, Akai J, Kimura A, Hiraoka M, Kitabatake A.

Cardiovasc Res. 2002 Feb 1;53(2):348-54.

PubMed [citation]
PMID:
11827685

Rapid, sensitive and inexpensive detection of SCN5A genetic variations by high resolution melting analysis.

Millat G, Chanavat V, Rodriguez-Lafrasse C, Rousson R.

Clin Biochem. 2009 Apr;42(6):491-9. doi: 10.1016/j.clinbiochem.2008.10.014. Epub 2008 Nov 6.

PubMed [citation]
PMID:
19026623
See all PubMed Citations (10)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004847789.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (10)

Description

The p.Ser1710Leu variant in SCN5A (also referred to as p.Ser1709Leu) has been reported in at least 6 individuals with features of SCN5A-associated disorders (Akai 2000, Shin 2007, Millat 2009, Makita 2012, Lee 2014, Lee 2016). This variant has also been reported in ClinVar (Variation ID 9383) and was identified in 1/113744 European and 3/34592 Latino chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In vitro functional studies support an impact on protein function (Akai 2000, Shirai 2002, Millat 2009). In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant SCN5A-associated disorders. ACMG/AMP Criteria applied: PM2, PS4_Moderate, PP3, PS3_Supporting.

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

Last Updated: Nov 10, 2024