NM_000335.5(SCN5A):c.2632C>T (p.Arg878Cys) AND Brugada syndrome

Clinical significance:Likely pathogenic (Last evaluated: Jul 8, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000058513.4

Allele description [Variation Report for NM_000335.5(SCN5A):c.2632C>T (p.Arg878Cys)]

NM_000335.5(SCN5A):c.2632C>T (p.Arg878Cys)

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.2632C>T (p.Arg878Cys)
Other names:
p.R878C:CGC>TGC
HGVS:
  • NC_000003.12:g.38585846G>A
  • NG_008934.1:g.68827C>T
  • NM_000335.5:c.2632C>TMANE SELECT
  • NM_001099404.2:c.2632C>T
  • NM_001099405.2:c.2632C>T
  • NM_001160160.2:c.2632C>T
  • NM_001160161.2:c.2632C>T
  • NM_001354701.2:c.2632C>T
  • NM_198056.2:c.2632C>T
  • NM_198056.3:c.2632C>T
  • NP_000326.2:p.Arg878Cys
  • NP_001092874.1:p.Arg878Cys
  • NP_001092875.1:p.Arg878Cys
  • NP_001153632.1:p.Arg878Cys
  • NP_001153633.1:p.Arg878Cys
  • NP_001341630.1:p.Arg878Cys
  • NP_932173.1:p.Arg878Cys
  • NP_932173.1:p.Arg878Cys
  • LRG_289t1:c.2632C>T
  • LRG_289:g.68827C>T
  • LRG_289p1:p.Arg878Cys
  • NC_000003.11:g.38627337G>A
  • Q14524:p.Arg878Cys
Protein change:
R878C
Links:
UniProtKB: Q14524#VAR_055183; dbSNP: rs199473168
NCBI 1000 Genomes Browser:
rs199473168
Molecular consequence:
  • NM_000335.5:c.2632C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.2632C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.2632C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.2632C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.2632C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.2632C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.2:c.2632C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.2632C>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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000090033Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trustno assertion providednot providedgermlineliterature only

PubMed (5)
[See all records that cite these PMIDs]

SCV001214073Invitaecriteria provided, single submitter
Likely pathogenic
(Jul 8, 2020)
germlineclinical testing

PubMed (9)
[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

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

Gene symbol: SCN5A. Disease: Brugada syndrome.

Crotti L, Ferrandi C, Pedrazzini M, Insolia R, Cuoretti A, Sanzo A, Dagradi F, De Ferrari GM, Schwartz PJ.

Hum Genet. 2008 Jun;123(5):542. No abstract available.

PubMed [citation]
PMID:
20960617
See all PubMed Citations (12)

Details of each submission

From Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust, SCV000090033.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (5)

Description

This variant has been reported as associated with Brugada syndrome in the following publications (PMID:18616619;PMID:20129283;PMID:20539757;PMID:20960617). 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 Invitae, SCV001214073.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

This sequence change replaces arginine with cysteine at codon 878 of the SCN5A protein (p.Arg878Cys). 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 observed in several individuals affected with Brugada syndrome (PMID: 26036855, 20960618, 28341781, 28781330, 18616619). ClinVar contains an entry for this variant (Variation ID: 67744). This variant has been reported to have conflicting or insufficient data to determine the effect on SCN5A protein function (PMID: 20539757, 18616619, 20384651, 22739120). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Oct 30, 2021

Support Center