NM_000335.5(SCN5A):c.5800G>A (p.Gly1934Ser) AND Brugada syndrome

Clinical significance:Uncertain significance (Last evaluated: Mar 26, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000058807.5

Allele description [Variation Report for NM_000335.5(SCN5A):c.5800G>A (p.Gly1934Ser)]

NM_000335.5(SCN5A):c.5800G>A (p.Gly1934Ser)

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.5800G>A (p.Gly1934Ser)
HGVS:
  • NC_000003.12:g.38550569C>T
  • NG_008934.1:g.104104G>A
  • NM_000335.5:c.5800G>AMANE SELECT
  • NM_001099404.2:c.5803G>A
  • NM_001099405.2:c.5749G>A
  • NM_001160160.2:c.5704G>A
  • NM_001160161.2:c.5641G>A
  • NM_001354701.2:c.5746G>A
  • NM_198056.3:c.5803G>A
  • NP_000326.2:p.Gly1934Ser
  • NP_001092874.1:p.Gly1935Ser
  • NP_001092875.1:p.Gly1917Ser
  • NP_001153632.1:p.Gly1902Ser
  • NP_001153633.1:p.Gly1881Ser
  • NP_001341630.1:p.Gly1916Ser
  • NP_932173.1:p.Gly1935Ser
  • NP_932173.1:p.Gly1935Ser
  • LRG_289t1:c.5803G>A
  • LRG_289:g.104104G>A
  • LRG_289p1:p.Gly1935Ser
  • NC_000003.11:g.38592060C>T
  • NM_198056.2:c.5803G>A
Protein change:
G1881S
Links:
dbSNP: rs199473637
NCBI 1000 Genomes Browser:
rs199473637
Molecular consequence:
  • NM_000335.5:c.5800G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.5803G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.5749G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.5704G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.5641G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.5746G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.5803G>A - 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
SCV000090327Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trustno assertion providednot providedgermlineliterature only

PubMed (4)
[See all records that cite these PMIDs]

SCV000812435Invitaecriteria provided, single submitter
Uncertain significance
(Mar 26, 2020)
germlineclinical testing

PubMed (6)
[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

Contribution of a KCNH2 variant in genotyped long QT syndrome: Romano-Ward syndrome under double mutations and acquired long QT syndrome under heterozygote.

Fujii Y, Matsumoto Y, Hayashi K, Ding WG, Tomita Y, Fukumoto D, Wada Y, Ichikawa M, Sonoda K, Ozawa J, Makiyama T, Ohno S, Yamagishi M, Matsuura H, Horie M, Itoh H.

J Cardiol. 2017 Jul;70(1):74-79. doi: 10.1016/j.jjcc.2016.09.010. Epub 2016 Nov 3.

PubMed [citation]
PMID:
27816319
See all PubMed Citations (7)

Details of each submission

From Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust, SCV000090327.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (4)

Description

This variant has been reported as associated with Brugada syndrome in the following publications (PMID:16267250;PMID:18508782;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 Invitae, SCV000812435.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change replaces glycine with serine at codon 1935 of the SCN5A protein (p.Gly1935Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs199473637, ExAC 0.01%). This variant has been reported in individual(s) with long QT syndrome, unexplained sudden death, and suspected or confirmed Brugada syndrome (PMID: 16267250, 27816319, 18508782, 20129283). ClinVar contains an entry for this variant (Variation ID: 68011). Experimental studies have shown that this missense change enhances the SCN5A channel slow inactivation (PMID: 16267250, 17854786). 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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