NM_000335.5(SCN5A):c.3953G>T (p.Gly1318Val) AND Long QT syndrome 3

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 4, 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:: RCV000709762.9

Allele description [Variation Report for NM_000335.5(SCN5A):c.3953G>T (p.Gly1318Val)]

NM_000335.5(SCN5A):c.3953G>T (p.Gly1318Val)

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.3953G>T (p.Gly1318Val)

HGVS:

NC_000003.12:g.38562422C>A
NG_008934.1:g.92251G>T
NM_000335.5:c.3953G>TMANE SELECT
NM_001099404.2:c.3956G>T
NM_001099405.2:c.3956G>T
NM_001160160.2:c.3953G>T
NM_001160161.2:c.3794G>T
NM_001354701.2:c.3953G>T
NM_198056.3:c.3956G>T
NP_000326.2:p.Gly1318Val
NP_001092874.1:p.Gly1319Val
NP_001092875.1:p.Gly1319Val
NP_001153632.1:p.Gly1318Val
NP_001153633.1:p.Gly1265Val
NP_001341630.1:p.Gly1318Val
NP_932173.1:p.Gly1319Val
NP_932173.1:p.Gly1319Val
LRG_289t1:c.3956G>T
LRG_289:g.92251G>T
LRG_289p1:p.Gly1319Val
NC_000003.11:g.38603913C>A
NM_198056.2:c.3956G>T
Q14524:p.Gly1319Val

Protein change:

G1265V

Links:

UniProtKB: Q14524#VAR_026375; dbSNP: rs199473220

NCBI 1000 Genomes Browser:

rs199473220

Molecular consequence:

NM_000335.5:c.3953G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.3956G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.3956G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.3953G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.3794G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.3953G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.3956G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Long QT syndrome 3 (LQT3)
Identifiers:: MONDO: MONDO:0011377; MedGen: C1859062; Orphanet: 101016; Orphanet: 768; OMIM: 603830

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000840065	Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 4, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000840065

Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 4, 2017)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine, SCV000840065.1

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

Description

The c.3956G>T (p.Gly1319Val) variant has been reported in several patients with Brugada syndrome [PMID 12106943, 19251209, 21273195]. Functional assays showed that this variant contributes to a reduction in sodium currents [PMID 17854786]. This variant was observed in only one individual at the heterozygous state in the ExAC population database (http://exac.broadinstitute.org/variant/3-38603913-C-A).This variant is conserved in mammals and while not clinically validated, computer-based algorithms (SIFT and Polyphen-2) predict this p.Gly1319Val change to be deleterious. This variant is thus classified as pathogenic. Pathogenic variants in SCN5A are also considered medically actionable [ACMG 59, PMID 27854360]

#	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 10, 2024

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