NM_000335.5(SCN5A):c.2182G>A (p.Val728Ile) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 16, 2020
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:: RCV002424779.9

Allele description [Variation Report for NM_000335.5(SCN5A):c.2182G>A (p.Val728Ile)]

NM_000335.5(SCN5A):c.2182G>A (p.Val728Ile)

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.2182G>A (p.Val728Ile)

HGVS:

NC_000003.12:g.38597809C>T
NG_008934.1:g.56864G>A
NM_000335.5:c.2182G>AMANE SELECT
NM_001099404.2:c.2182G>A
NM_001099405.2:c.2182G>A
NM_001160160.2:c.2182G>A
NM_001160161.2:c.2182G>A
NM_001354701.2:c.2182G>A
NM_198056.3:c.2182G>A
NP_000326.2:p.Val728Ile
NP_000326.2:p.Val728Ile
NP_001092874.1:p.Val728Ile
NP_001092875.1:p.Val728Ile
NP_001153632.1:p.Val728Ile
NP_001153633.1:p.Val728Ile
NP_001341630.1:p.Val728Ile
NP_932173.1:p.Val728Ile
NP_932173.1:p.Val728Ile
LRG_289t1:c.2182G>A
LRG_289t2:c.2182G>A
LRG_289:g.56864G>A
LRG_289p1:p.Val728Ile
LRG_289p2:p.Val728Ile
NC_000003.11:g.38639300C>T
NM_000335.4:c.2182G>A
NM_198056.2:c.2182G>A

Protein change:

V728I

Links:

dbSNP: rs958480279

NCBI 1000 Genomes Browser:

rs958480279

Molecular consequence:

NM_000335.5:c.2182G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.2182G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.2182G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.2182G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.2182G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.2182G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.2182G>A - 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
SCV002729379	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Mar 16, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22984773, 30662450 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002729379

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Mar 16, 2020)

germline

clinical testing

PubMed (2)
[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

A study of the SCN5A gene in a cohort of 76 patients with Brugada syndrome.

García-Molina E, Lacunza J, Ruiz-Espejo F, Sabater M, García-Alberola A, Gimeno JR, Cañizares F, García A, Martínez P, Valdés M, Tovar I.

Clin Genet. 2013 Jun;83(6):530-8. doi: 10.1111/cge.12017. Epub 2012 Oct 16.

PubMed [citation]

PMID:: 22984773

Impact of Ancestral Differences and Reassessment of the Classification of Previously Reported Pathogenic Variants in Patients With Brugada Syndrome in the Genomic Era: A SADS-TW BrS Registry.

Chen CJ, Lu TP, Lin LY, Liu YB, Ho LT, Huang HC, Lai LP, Hwang JJ, Yeh SS, Wu CK, Juang JJ, Antzelevitch C.

Front Genet. 2018;9:680. doi: 10.3389/fgene.2018.00680.

PubMed [citation]

PMID:: 30662450
PMCID:: PMC6328444

Details of each submission

From Ambry Genetics, SCV002729379.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The p.V728I variant (also known as c.2182G>A), located in coding exon 13 of the SCN5A gene, results from a G to A substitution at nucleotide position 2182. The valine at codon 728 is replaced by isoleucine, an amino acid with highly similar properties. This variant has been reported in an asymptomatic patient in a Brugada syndrome cohort (García-Molina E et al. Clin. Genet., 2013 Jun;83:530-8). This amino acid position is well conserved in available vertebrate species; however, isoleucine is the reference amino acid in other 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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