NM_198056.2(SCN5A):c.1604G>A (p.Arg535Gln) AND Brugada syndrome

Clinical significance:Uncertain significance (Last evaluated: Nov 22, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000638649.1

Allele description [Variation Report for NM_198056.2(SCN5A):c.1604G>A (p.Arg535Gln)]

NM_198056.2(SCN5A):c.1604G>A (p.Arg535Gln)

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_198056.2(SCN5A):c.1604G>A (p.Arg535Gln)
HGVS:
  • NC_000003.12:g.38603998C>T
  • NG_008934.1:g.50675G>A
  • NM_000335.4:c.1604G>A
  • NM_001099404.1:c.1604G>A
  • NM_001099405.1:c.1604G>A
  • NM_001160160.2:c.1604G>A
  • NM_001160161.1:c.1604G>A
  • NM_001354701.2:c.1604G>A
  • NM_198056.2:c.1604G>A
  • NP_000326.2:p.Arg535Gln
  • NP_001092874.1:p.Arg535Gln
  • NP_001092875.1:p.Arg535Gln
  • NP_001153632.1:p.Arg535Gln
  • NP_001153633.1:p.Arg535Gln
  • NP_001341630.1:p.Arg535Gln
  • NP_932173.1:p.Arg535Gln
  • LRG_289t1:c.1604G>A
  • LRG_289t2:c.1604G>A
  • LRG_289t3:c.1604G>A
  • LRG_289:g.50675G>A
  • LRG_289p1:p.Arg535Gln
  • LRG_289p2:p.Arg535Gln
  • LRG_289p3:p.Arg535Gln
  • NC_000003.11:g.38645489C>T
  • Q14524:p.Arg535Gln
Protein change:
R535Q
Links:
UniProtKB: Q14524#VAR_074713; dbSNP: rs199473121
NCBI 1000 Genomes Browser:
rs199473121
Molecular consequence:
  • NM_000335.4:c.1604G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.1:c.1604G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.1:c.1604G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.1604G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.1:c.1604G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.1604G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.2:c.1604G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Brugada syndrome
Synonyms:
Sudden unexplained nocturnal death syndrome; Sudden Unexplained Death Syndrome; Sudden Unexplained Nocturnal Death Syndrome (SUNDS)
Identifiers:
MedGen: C1142166; OMIM: PS601144

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000760187Invitaecriteria provided, single submitter
Uncertain significance
(Nov 22, 2017)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test.

Kapplinger JD, Tester DJ, Salisbury BA, Carr JL, Harris-Kerr C, Pollevick GD, Wilde AA, Ackerman MJ.

Heart Rhythm. 2009 Sep;6(9):1297-303. doi: 10.1016/j.hrthm.2009.05.021. Epub 2009 Jun 23.

PubMed [citation]
PMID:
19716085
PMCID:
PMC3049907

The disease-specific phenotype in cardiomyocytes derived from induced pluripotent stem cells of two long QT syndrome type 3 patients.

Fatima A, Kaifeng S, Dittmann S, Xu G, Gupta MK, Linke M, Zechner U, Nguemo F, Milting H, Farr M, Hescheler J, Sarić T.

PLoS One. 2013;8(12):e83005. doi: 10.1371/journal.pone.0083005.

PubMed [citation]
PMID:
24349418
PMCID:
PMC3859612
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000760187.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces arginine with glutamine at codon 535 of the SCN5A protein (p.Arg535Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs199473121, ExAC 0.002%). This variant has been reported in several individuals either affected with long QT syndrome or with a suspicion of this condition (PMID: 24349418, 19716085). ClinVar contains an entry for this variant (Variation ID: 67672). Experimental studies have shown that this missense change results in a sodium channel with an increased inactivation time leading to a persistent sodium current and a tendency to prolonged action potential duration (PMID: 24349418). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Nov 2, 2019

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