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NM_000335.5(SCN5A):c.611C>T (p.Ala204Val) AND Brugada syndrome

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Sep 22, 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:
RCV000058828.5

Allele description [Variation Report for NM_000335.5(SCN5A):c.611C>T (p.Ala204Val)]

NM_000335.5(SCN5A):c.611C>T (p.Ala204Val)

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.611C>T (p.Ala204Val)
HGVS:
  • NC_000003.12:g.38620843G>A
  • NG_008934.1:g.33830C>T
  • NM_000335.5:c.611C>TMANE SELECT
  • NM_001099404.2:c.611C>T
  • NM_001099405.2:c.611C>T
  • NM_001160160.2:c.611C>T
  • NM_001160161.2:c.611C>T
  • NM_001354701.2:c.611C>T
  • NM_198056.3:c.611C>T
  • NP_000326.2:p.Ala204Val
  • NP_001092874.1:p.Ala204Val
  • NP_001092875.1:p.Ala204Val
  • NP_001153632.1:p.Ala204Val
  • NP_001153633.1:p.Ala204Val
  • NP_001341630.1:p.Ala204Val
  • NP_932173.1:p.Ala204Val
  • NP_932173.1:p.Ala204Val
  • LRG_289t1:c.611C>T
  • LRG_289:g.33830C>T
  • LRG_289p1:p.Ala204Val
  • NC_000003.11:g.38662334G>A
  • NM_198056.2:c.611C>T
  • NM_198056.3:c.611C>T
  • Q14524:p.Ala204Val
Protein change:
A204V
Links:
UniProtKB: Q14524#VAR_074330; dbSNP: rs199473559
NCBI 1000 Genomes Browser:
rs199473559
Molecular consequence:
  • NM_000335.5:c.611C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.611C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.611C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.611C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.611C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.611C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.611C>T - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
functionally_normal [Sequence Ontology: SO:0002219] - Comment(s)

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
SCV000090348Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust
no classification provided
not providedgermlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

SCV001410436Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Sep 22, 2019)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing, literature only

Citations

PubMed

Paralogous annotation of disease-causing variants in long QT syndrome genes.

Ware JS, Walsh R, Cunningham F, Birney E, Cook SA.

Hum Mutat. 2012 Aug;33(8):1188-1191. doi: 10.1002/humu.22114. Epub 2012 Jun 7.

PubMed [citation]
PMID:
22581653
PMCID:
PMC4640174

An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing.

Kapplinger JD, Tester DJ, Alders M, Benito B, Berthet M, Brugada J, Brugada P, Fressart V, Guerchicoff A, Harris-Kerr C, Kamakura S, Kyndt F, Koopmann TT, Miyamoto Y, Pfeiffer R, Pollevick GD, Probst V, Zumhagen S, Vatta M, Towbin JA, Shimizu W, Schulze-Bahr E, et al.

Heart Rhythm. 2010 Jan;7(1):33-46. doi: 10.1016/j.hrthm.2009.09.069. Epub 2009 Oct 8.

PubMed [citation]
PMID:
20129283
PMCID:
PMC2822446
See all PubMed Citations (3)

Details of each submission

From Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust, SCV000090348.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

This variant has been reported as associated with Brugada syndrome in the following publications (PMID:20129283). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001410436.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces alanine with valine at codon 204 of the SCN5A protein (p.Ala204Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in an individual referred for diagnostic testing for Brugada syndrome (PMID: 20129283). ClinVar contains an entry for this variant (Variation ID: 68028). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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: Sep 29, 2024