NM_000335.5(SCN5A):c.1963G>A (p.Glu655Lys) AND Brugada syndrome

Clinical significance:Uncertain significance (Last evaluated: Feb 21, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001062666.2

Allele description [Variation Report for NM_000335.5(SCN5A):c.1963G>A (p.Glu655Lys)]

NM_000335.5(SCN5A):c.1963G>A (p.Glu655Lys)

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.1963G>A (p.Glu655Lys)
HGVS:
  • NC_000003.12:g.38598978C>T
  • NG_008934.1:g.55695G>A
  • NM_000335.5:c.1963G>AMANE SELECT
  • NM_001099404.2:c.1963G>A
  • NM_001099405.2:c.1963G>A
  • NM_001160160.2:c.1963G>A
  • NM_001160161.2:c.1963G>A
  • NM_001354701.2:c.1963G>A
  • NM_198056.2:c.1963G>A
  • NM_198056.3:c.1963G>A
  • NP_000326.2:p.Glu655Lys
  • NP_001092874.1:p.Glu655Lys
  • NP_001092875.1:p.Glu655Lys
  • NP_001153632.1:p.Glu655Lys
  • NP_001153633.1:p.Glu655Lys
  • NP_001341630.1:p.Glu655Lys
  • NP_932173.1:p.Glu655Lys
  • NP_932173.1:p.Glu655Lys
  • LRG_289t1:c.1963G>A
  • LRG_289:g.55695G>A
  • LRG_289p1:p.Glu655Lys
  • NC_000003.11:g.38640469C>T
  • Q14524:p.Glu655Lys
Protein change:
E655K; GLU655LYS
Links:
UniProtKB: Q14524#VAR_055180; OMIM: 600163.0045; dbSNP: rs199473579
NCBI 1000 Genomes Browser:
rs199473579
Molecular consequence:
  • NM_000335.5:c.1963G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.1963G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.1963G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.1963G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.1963G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.1963G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.2:c.1963G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.1963G>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
SCV001227481Invitaecriteria provided, single submitter
Uncertain significance
(Feb 21, 2020)
germlineclinical testing

PubMed (2)
[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

Cardiac sodium channel (SCN5A) variants associated with atrial fibrillation.

Darbar D, Kannankeril PJ, Donahue BS, Kucera G, Stubblefield T, Haines JL, George AL Jr, Roden DM.

Circulation. 2008 Apr 15;117(15):1927-35. doi: 10.1161/CIRCULATIONAHA.107.757955. Epub 2008 Mar 31.

PubMed [citation]
PMID:
18378609
PMCID:
PMC2365761

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001227481.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces glutamic acid with lysine at codon 655 of the SCN5A protein (p.Glu655Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with atrial fibrillation in a family (PMID: 18378609). ClinVar contains an entry for this variant (Variation ID: 30049). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). 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: Oct 30, 2021

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