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NM_000335.5(SCN5A):c.6031C>T (p.Arg2011Cys) AND Cardiac arrhythmia

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Dec 18, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001842404.12

Allele description [Variation Report for NM_000335.5(SCN5A):c.6031C>T (p.Arg2011Cys)]

NM_000335.5(SCN5A):c.6031C>T (p.Arg2011Cys)

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.6031C>T (p.Arg2011Cys)
HGVS:
  • NC_000003.12:g.38550338G>A
  • NG_008934.1:g.104335C>T
  • NM_000335.5:c.6031C>TMANE SELECT
  • NM_001099404.2:c.6034C>T
  • NM_001099405.2:c.5980C>T
  • NM_001160160.2:c.5935C>T
  • NM_001160161.2:c.5872C>T
  • NM_001354701.2:c.5977C>T
  • NM_198056.3:c.6034C>T
  • NP_000326.2:p.Arg2011Cys
  • NP_001092874.1:p.Arg2012Cys
  • NP_001092875.1:p.Arg1994Cys
  • NP_001153632.1:p.Arg1979Cys
  • NP_001153633.1:p.Arg1958Cys
  • NP_001341630.1:p.Arg1993Cys
  • NP_932173.1:p.Arg2012Cys
  • NP_932173.1:p.Arg2012Cys
  • LRG_289t1:c.6034C>T
  • LRG_289:g.104335C>T
  • LRG_289p1:p.Arg2012Cys
  • NC_000003.11:g.38591829G>A
  • NM_198056.2:c.6034C>T
  • Q14524:p.Arg2012Cys
Protein change:
R1958C
Links:
UniProtKB: Q14524#VAR_074764; dbSNP: rs199473640
NCBI 1000 Genomes Browser:
rs199473640
Molecular consequence:
  • NM_000335.5:c.6031C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.6034C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.5980C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.5935C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.5872C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.5977C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.6034C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
14

Condition(s)

Name:
Cardiac arrhythmia
Synonyms:
Cardiac rhythm disease
Identifiers:
EFO: EFO_0004269; MONDO: MONDO:0007263; MedGen: C0003811; Human Phenotype Ontology: HP:0011675

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000904480Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Apr 3, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV004831380All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Dec 18, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown14not providednot provided108544not providedclinical testing

Citations

PubMed

Novel sodium channel SCN5A mutations in Brugada syndrome patients from Greece.

Kotta CM, Anastasakis A, Gatzoulis K, Manolis AS, Stefanadis C.

Int J Cardiol. 2010 Nov 5;145(1):45-8. doi: 10.1016/j.ijcard.2009.03.134. Epub 2009 Apr 29.

PubMed [citation]
PMID:
19406494

Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test.

Kapplinger JD, Tester DJ, Salisbury BA, Carr JL, Harris-Kerr C, Pollevick GD, Wilde AA, Ackerman MJ.

Heart Rhythm. 2009 Sep;6(9):1297-303. doi: 10.1016/j.hrthm.2009.05.021. Epub 2009 Jun 23.

PubMed [citation]
PMID:
19716085
PMCID:
PMC3049907
See all PubMed Citations (3)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000904480.4

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

Description

This missense variant replaces arginine with cysteine at codon 2012 of the SCN5A protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual suspected to be affected with long QT syndrome (PMID: 19716085), as well as in a control individual (PMID: 19406494). This variant has been identified in 8/187482 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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

From All of Us Research Program, National Institutes of Health, SCV004831380.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided14not providednot providedclinical testing PubMed (3)

Description

This missense variant replaces arginine with cysteine at codon 2012 of the SCN5A protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual suspected to be affected with long QT syndrome (PMID: 19716085), as well as in a control individual (PMID: 19406494). This variant has been identified in 8/187482 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided14not providednot providednot provided

Last Updated: May 1, 2024