NM_000335.5(SCN5A):c.5735G>A (p.Arg1912His) AND Brugada syndrome

Clinical significance:Uncertain significance (Last evaluated: Sep 2, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001202604.2

Allele description [Variation Report for NM_000335.5(SCN5A):c.5735G>A (p.Arg1912His)]

NM_000335.5(SCN5A):c.5735G>A (p.Arg1912His)

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.5735G>A (p.Arg1912His)
Other names:
p.R1913H:CGC>CAC
HGVS:
  • NC_000003.12:g.38550634C>T
  • NG_008934.1:g.104039G>A
  • NM_000335.5:c.5735G>AMANE SELECT
  • NM_001099404.2:c.5738G>A
  • NM_001099405.2:c.5684G>A
  • NM_001160160.2:c.5639G>A
  • NM_001160161.2:c.5576G>A
  • NM_001354701.2:c.5681G>A
  • NM_198056.3:c.5738G>A
  • NP_000326.2:p.Arg1912His
  • NP_001092874.1:p.Arg1913His
  • NP_001092875.1:p.Arg1895His
  • NP_001153632.1:p.Arg1880His
  • NP_001153633.1:p.Arg1859His
  • NP_001341630.1:p.Arg1894His
  • NP_932173.1:p.Arg1913His
  • NP_932173.1:p.Arg1913His
  • LRG_289t1:c.5738G>A
  • LRG_289:g.104039G>A
  • LRG_289p1:p.Arg1913His
  • NC_000003.11:g.38592125C>T
  • NM_198056.2:c.5738G>A
  • Q14524:p.Arg1913His
Protein change:
R1859H
Links:
UniProtKB: Q14524#VAR_074762; dbSNP: rs199473327
NCBI 1000 Genomes Browser:
rs199473327
Molecular consequence:
  • NM_000335.5:c.5735G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.5738G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.5684G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.5639G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.5576G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.5681G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.5738G>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
SCV001373721Invitaecriteria provided, single submitter
Uncertain significance
(Sep 2, 2020)
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

Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice.

Napolitano C, Priori SG, Schwartz PJ, Bloise R, Ronchetti E, Nastoli J, Bottelli G, Cerrone M, Leonardi S.

JAMA. 2005 Dec 21;294(23):2975-80.

PubMed [citation]
PMID:
16414944

Prospective evaluation of the familial prevalence of the brugada syndrome.

Hermida JS, Dassonvalle E, Six I, Amant C, Coviaux F, Clerc J, Herent D, Hermida A, Rochette J, Jarry G.

Am J Cardiol. 2010 Dec 15;106(12):1758-62. doi: 10.1016/j.amjcard.2010.07.049.

PubMed [citation]
PMID:
21126620
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001373721.2

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

Description

This sequence change replaces arginine with histidine at codon 1913 of the SCN5A protein (p.Arg1913His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs199473327, ExAC 0.03%). This variant has been observed in individuals with clinical features of SCN5A-related conditions, but has also been observed in at least one unaffected family member (PMID: 16414944, 21126620). ClinVar contains an entry for this variant (Variation ID: 68009). 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: Dec 4, 2021

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