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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 27, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003162461.8

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]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003903679	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Uncertain significance (Feb 27, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 19406494, 19716085, 30847666, 31737537, 32893267 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003903679

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Uncertain significance
(Feb 27, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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 (5)

Details of each submission

From Ambry Genetics, SCV003903679.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

The p.R2012C variant (also known as c.6034C>T), located in coding exon 27 of the SCN5A gene, results from a C to T substitution at nucleotide position 6034. The arginine at codon 2012 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported in long QT syndrome cohorts, a Brugada syndrome cohort, and an arrhythmia genetic testing cohort; however, clinical details were limited in these cases (Kapplinger JD et al. Heart Rhythm, 2009 Sep;6:1297-303; Kotta CM et al. Int J Cardiol, 2010 Nov;145:45-8; Marschall C et al. Cardiovasc Diagn Ther, 2019 Oct;9:S292-S298; van Lint FHM et al. Neth Heart J, 2019 Jun;27:304-309; Walsh R et al. Genet Med, 2021 Jan;23:47-58). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 24, 2024

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