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:

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

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

SCN5A:sodium voltage-gated channel alpha subunit 5 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000335.5(SCN5A):c.2632C>T (p.Arg878Cys)
Other names:
  • 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:
UniProtKB: Q14524#VAR_055183; dbSNP: rs199473168
NCBI 1000 Genomes Browser:
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]


Brugada syndrome
Sudden unexpected nocturnal death syndrome; Sudden unexplained nocturnal death syndrome; Sudden Unexplained Death Syndrome; See all synonyms [MedGen]
MONDO: MONDO:0015263; MedGen: C1142166; OMIM: PS601144

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
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



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]

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]
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)


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.

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)


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.

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

Last Updated: Oct 30, 2021

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