NM_000335.5(SCN5A):c.1567C>T (p.Arg523Cys) AND Brugada syndrome

Clinical significance:Uncertain significance (Last evaluated: May 7, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000464270.2

Allele description [Variation Report for NM_000335.5(SCN5A):c.1567C>T (p.Arg523Cys)]

NM_000335.5(SCN5A):c.1567C>T (p.Arg523Cys)

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.1567C>T (p.Arg523Cys)
HGVS:
  • NC_000003.12:g.38604035G>A
  • NG_008934.1:g.50638C>T
  • NM_000335.5:c.1567C>TMANE SELECT
  • NM_001099404.2:c.1567C>T
  • NM_001099405.2:c.1567C>T
  • NM_001160160.2:c.1567C>T
  • NM_001160161.2:c.1567C>T
  • NM_001354701.2:c.1567C>T
  • NM_198056.3:c.1567C>T
  • NP_000326.2:p.Arg523Cys
  • NP_001092874.1:p.Arg523Cys
  • NP_001092875.1:p.Arg523Cys
  • NP_001092875.1:p.Arg523Cys
  • NP_001153632.1:p.Arg523Cys
  • NP_001153633.1:p.Arg523Cys
  • NP_001341630.1:p.Arg523Cys
  • NP_932173.1:p.Arg523Cys
  • NP_932173.1:p.Arg523Cys
  • LRG_289t1:c.1567C>T
  • LRG_289:g.50638C>T
  • LRG_289p1:p.Arg523Cys
  • NC_000003.11:g.38645526G>A
  • NM_001099405.1:c.1567C>T
  • NM_198056.2:c.1567C>T
Protein change:
R523C
Links:
dbSNP: rs199473119
NCBI 1000 Genomes Browser:
rs199473119
Molecular consequence:
  • NM_000335.5:c.1567C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.1567C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.1567C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.1567C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.1567C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.1567C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.1567C>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
SCV000545031Invitaecriteria provided, single submitter
Uncertain significance
(May 7, 2018)
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

Molecular genetic analysis of long QT syndrome in Norway indicating a high prevalence of heterozygous mutation carriers.

Berge KE, Haugaa KH, Früh A, Anfinsen OG, Gjesdal K, Siem G, Oyen N, Greve G, Carlsson A, Rognum TO, Hallerud M, Kongsgård E, Amlie JP, Leren TP.

Scand J Clin Lab Invest. 2008;68(5):362-8. doi: 10.1080/00365510701765643.

PubMed [citation]
PMID:
18752142

New SCN5A mutation in a SUDEP victim with idiopathic epilepsy.

Aurlien D, Leren TP, Taubøll E, Gjerstad L.

Seizure. 2009 Mar;18(2):158-60. doi: 10.1016/j.seizure.2008.07.008. Epub 2008 Aug 27.

PubMed [citation]
PMID:
18752973
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000545031.3

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

Description

This sequence change replaces arginine with cysteine at codon 523 of the SCN5A protein (p.Arg523Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in a individual referred for long QT syndrome testing and another individual with epilepsy who died unexpectedly. Currently there is insufficient evidence to conclude whether this variant segregates with disease or not (PMID: 18752142, 18752973). ClinVar contains an entry for this variant (Variation ID: 67667). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). 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: Dec 4, 2021

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