NM_000335.5(SCN5A):c.2977G>A (p.Ala993Thr) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 29, 2022
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:: RCV002438346.2

Allele description [Variation Report for NM_000335.5(SCN5A):c.2977G>A (p.Ala993Thr)]

NM_000335.5(SCN5A):c.2977G>A (p.Ala993Thr)

Genes:

LOC110121269:VISTA enhancer hs2177 [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.2977G>A (p.Ala993Thr)

HGVS:

NC_000003.12:g.38581182C>T
NG_008934.1:g.73491G>A
NG_053884.1:g.2921C>T
NM_000335.5:c.2977G>AMANE SELECT
NM_001099404.2:c.2977G>A
NM_001099405.2:c.2977G>A
NM_001160160.2:c.2977G>A
NM_001160161.2:c.2977G>A
NM_001354701.2:c.2977G>A
NM_198056.3:c.2977G>A
NP_000326.2:p.Ala993Thr
NP_001092874.1:p.Ala993Thr
NP_001092875.1:p.Ala993Thr
NP_001153632.1:p.Ala993Thr
NP_001153633.1:p.Ala993Thr
NP_001341630.1:p.Ala993Thr
NP_932173.1:p.Ala993Thr
NP_932173.1:p.Ala993Thr
LRG_289t1:c.2977G>A
LRG_289:g.73491G>A
LRG_289p1:p.Ala993Thr
NC_000003.11:g.38622673C>T
NM_198056.2:c.2977G>A
p.Ala993Thr

Protein change:

A993T

Links:

dbSNP: rs770088052

NCBI 1000 Genomes Browser:

rs770088052

Molecular consequence:

NM_000335.5:c.2977G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.2977G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.2977G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.2977G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.2977G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.2977G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.2977G>A - 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

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002746212	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jun 29, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27287068, 31696929, 32893267 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002746212

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jun 29, 2022)

germline

clinical testing

PubMed (3)
[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

Electrophysiological characterization of a large set of novel variants in the SCN5A-gene: identification of novel LQTS3 and BrS mutations.

Ortiz-Bonnin B, Rinné S, Moss R, Streit AK, Scharf M, Richter K, Stöber A, Pfeufer A, Seemann G, Kääb S, Beckmann BM, Decher N.

Pflugers Arch. 2016 Aug;468(8):1375-87. doi: 10.1007/s00424-016-1844-3. Epub 2016 Jun 11.

PubMed [citation]

PMID:: 27287068

Variant frequencies of KCNQ1, KCNH2, and SCN5A in a Chinese inherited arrhythmia cohort and other disease cohorts undergoing genetic testing.

Li X, Liu N, Bai R.

Ann Hum Genet. 2020 Mar;84(2):161-168. doi: 10.1111/ahg.12359. Epub 2019 Nov 7.

PubMed [citation]

PMID:: 31696929

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002746212.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The p.A993T variant (also known as c.2977G>A), located in coding exon 16 of the SCN5A gene, results from a G to A substitution at nucleotide position 2977. The alanine at codon 993 is replaced by threonine, an amino acid with similar properties. This variant was detected in an individual with prolonged QTc, as well as in her mother whose QTc value was in the upper range of normal (Ortiz-Bonnin B et al. Pflugers Arch, 2016 08;468:1375-87). This variant has also been reported in epilepsy and long QT syndrome cohorts with limited clinical details provided (Li X et al. Ann Hum Genet, 2020 03;84:161-168; Walsh R et al. Genet Med, 2021 01;23:47-58). Limited functional studies suggested some increase in peak current amplitude and slowed inactivation kinetics; however, the clinical consequences of these findings are uncertain (Ortiz-Bonnin B et al. Pflugers Arch, 2016 08;468:1375-87). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated 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

ClinVar

Relating variation to medicine