U.S. flag

An official website of the United States government

NM_000335.5(SCN5A):c.4294G>T (p.Gly1432Trp) AND Cardiovascular phenotype

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 8, 2017
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:
RCV000620033.3

Allele description [Variation Report for NM_000335.5(SCN5A):c.4294G>T (p.Gly1432Trp)]

NM_000335.5(SCN5A):c.4294G>T (p.Gly1432Trp)

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.4294G>T (p.Gly1432Trp)
HGVS:
  • NC_000003.12:g.38557233C>A
  • NG_008934.1:g.97440G>T
  • NM_000335.5:c.4294G>TMANE SELECT
  • NM_001099404.2:c.4297G>T
  • NM_001099405.2:c.4246-655G>T
  • NM_001160160.2:c.4294G>T
  • NM_001160161.2:c.4135G>T
  • NM_001354701.2:c.4243-655G>T
  • NM_198056.3:c.4297G>T
  • NP_000326.2:p.Gly1432Trp
  • NP_001092874.1:p.Gly1433Trp
  • NP_001153632.1:p.Gly1432Trp
  • NP_001153633.1:p.Gly1379Trp
  • NP_932173.1:p.Gly1433Trp
  • NP_932173.1:p.Gly1433Trp
  • LRG_289t1:c.4297G>T
  • LRG_289:g.97440G>T
  • LRG_289p1:p.Gly1433Trp
  • NC_000003.11:g.38598724C>A
  • NM_198056.2:c.4297G>T
Protein change:
G1379W
Links:
dbSNP: rs867001670
NCBI 1000 Genomes Browser:
rs867001670
Molecular consequence:
  • NM_001099405.2:c.4246-655G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354701.2:c.4243-655G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000335.5:c.4294G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.4297G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.4294G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.4135G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.4297G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000737940Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Mar 8, 2017) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing.

Kapplinger JD, Tester DJ, Alders M, Benito B, Berthet M, Brugada J, Brugada P, Fressart V, Guerchicoff A, Harris-Kerr C, Kamakura S, Kyndt F, Koopmann TT, Miyamoto Y, Pfeiffer R, Pollevick GD, Probst V, Zumhagen S, Vatta M, Towbin JA, Shimizu W, Schulze-Bahr E, et al.

Heart Rhythm. 2010 Jan;7(1):33-46. doi: 10.1016/j.hrthm.2009.09.069. Epub 2009 Oct 8.

PubMed [citation]
PMID:
20129283
PMCID:
PMC2822446

A heterozygous missense SCN5A mutation associated with early repolarization syndrome.

Li N, Wang R, Hou C, Zhang Y, Teng S, Pu J.

Int J Mol Med. 2013 Sep;32(3):661-7. doi: 10.3892/ijmm.2013.1422. Epub 2013 Jun 21.

PubMed [citation]
PMID:
23799537

Details of each submission

From Ambry Genetics, SCV000737940.5

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

Description

The p.G1433W variant (also known as c.4297G>T), located in coding exon 23 of the SCN5A gene, results from a G to T substitution at nucleotide position 4297. The glycine at codon 1433 is replaced by tryptophan, an amino acid with highly dissimilar properties. This variant has not been described in the literature to date; however, other alterations involving the same amino acid, p.G1433V (c.4298G>T) and p.G1433R (c.4297G>C), either have been reported in a study of Brugada syndrome clinical genetic testing, although clinical details were limited (Kapplinger JD et al. Heart Rhythm. 2010;7:33-46), or in a patient with early repolarization syndrome (Li N et al. Int J Mol Med. 2013;32:661-7). This amino acid position is not well conserved in available vertebrate species. In addition, p.G1433W is predicted to be probably damaging and deleterious by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: May 1, 2024