NM_198056.2(SCN5A):c.3392C>T (p.Thr1131Ile) AND Brugada syndrome

Clinical significance:Uncertain significance (Last evaluated: Jun 30, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000468996.3

Allele description [Variation Report for NM_198056.2(SCN5A):c.3392C>T (p.Thr1131Ile)]

NM_198056.2(SCN5A):c.3392C>T (p.Thr1131Ile)

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.3392C>T (p.Thr1131Ile)
Other names:
p.T1131I:ACC>ATC
HGVS:
  • NC_000003.12:g.38576780G>A
  • NG_008934.1:g.77893C>T
  • NM_000335.4:c.3389C>T
  • NM_001099404.1:c.3392C>T
  • NM_001099405.1:c.3392C>T
  • NM_001160160.2:c.3389C>T
  • NM_001160161.1:c.3230C>T
  • NM_001354701.2:c.3389C>T
  • NM_198056.2:c.3392C>T
  • NP_000326.2:p.Thr1130Ile
  • NP_001092874.1:p.Thr1131Ile
  • NP_001092875.1:p.Thr1131Ile
  • NP_001153632.1:p.Thr1130Ile
  • NP_001153633.1:p.Thr1077Ile
  • NP_001341630.1:p.Thr1130Ile
  • NP_932173.1:p.Thr1131Ile
  • LRG_289t1:c.3392C>T
  • LRG_289t2:c.3389C>T
  • LRG_289t3:c.3392C>T
  • LRG_289:g.77893C>T
  • LRG_289p1:p.Thr1131Ile
  • LRG_289p2:p.Thr1130Ile
  • LRG_289p3:p.Thr1131Ile
  • NC_000003.11:g.38618271G>A
  • Q14524:p.Thr1131Ile
Protein change:
T1077I
Links:
UniProtKB: Q14524#VAR_055186; dbSNP: rs199473197
NCBI 1000 Genomes Browser:
rs199473197
Molecular consequence:
  • NM_000335.4:c.3389C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.1:c.3392C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.1:c.3392C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.3389C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.1:c.3230C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.3389C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.2:c.3392C>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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000545083Invitaecriteria provided, single submitter
Uncertain significance
(Jun 30, 2020)
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

Cardiac sodium channel (SCN5A) variants associated with atrial fibrillation.

Darbar D, Kannankeril PJ, Donahue BS, Kucera G, Stubblefield T, Haines JL, George AL Jr, Roden DM.

Circulation. 2008 Apr 15;117(15):1927-35. doi: 10.1161/CIRCULATIONAHA.107.757955. Epub 2008 Mar 31.

PubMed [citation]
PMID:
18378609
PMCID:
PMC2365761

Cardiac channelopathy testing in 274 ethnically diverse sudden unexplained deaths.

Wang D, Shah KR, Um SY, Eng LS, Zhou B, Lin Y, Mitchell AA, Nicaj L, Prinz M, McDonald TV, Sampson BA, Tang Y.

Forensic Sci Int. 2014 Apr;237:90-9. doi: 10.1016/j.forsciint.2014.01.014. Epub 2014 Feb 15.

PubMed [citation]
PMID:
24631775
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000545083.4

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

Description

This sequence change replaces threonine with isoleucine at codon 1131 of the SCN5A protein (p.Thr1131Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs199473197, ExAC 0.04%). This variant has been reported in an individual affected with atrial fibrillation who also presented with left atrial and left ventricular enlargements and in a case of sudden infant death (PMID: 18378609, 24631775). ClinVar contains an entry for this variant (Variation ID: 67795). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. 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: Oct 16, 2021

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