NM_000335.5(SCN5A):c.1190T>C (p.Ile397Thr) AND Cardiac arrhythmia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 2, 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:: RCV003996523.2

Allele description [Variation Report for NM_000335.5(SCN5A):c.1190T>C (p.Ile397Thr)]

NM_000335.5(SCN5A):c.1190T>C (p.Ile397Thr)

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.1190T>C (p.Ile397Thr)

HGVS:

NC_000003.12:g.38606099A>G
NG_008934.1:g.48574T>C
NM_000335.5:c.1190T>CMANE SELECT
NM_001099404.2:c.1190T>C
NM_001099405.2:c.1190T>C
NM_001160160.2:c.1190T>C
NM_001160161.2:c.1190T>C
NM_001354701.2:c.1190T>C
NM_198056.3:c.1190T>C
NP_000326.2:p.Ile397Thr
NP_001092874.1:p.Ile397Thr
NP_001092875.1:p.Ile397Thr
NP_001153632.1:p.Ile397Thr
NP_001153633.1:p.Ile397Thr
NP_001341630.1:p.Ile397Thr
NP_932173.1:p.Ile397Thr
NP_932173.1:p.Ile397Thr
LRG_289t1:c.1190T>C
LRG_289:g.48574T>C
LRG_289p1:p.Ile397Thr
NC_000003.11:g.38647590A>G
NM_198056.2:c.1190T>C
Q14524:p.Ile397Thr

Protein change:

I397T

Links:

UniProtKB: Q14524#VAR_074706; dbSNP: rs199473105

NCBI 1000 Genomes Browser:

rs199473105

Molecular consequence:

NM_000335.5:c.1190T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.1190T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.1190T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.1190T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.1190T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.1190T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.1190T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Cardiac arrhythmia
Synonyms:: Cardiac rhythm disease
Identifiers:: EFO: EFO_0004269; MONDO: MONDO:0007263; MedGen: C0003811; Human Phenotype Ontology: HP:0011675

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
SCV004841146	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Oct 2, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19716085, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004841146

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Oct 2, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

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

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 All of Us Research Program, National Institutes of Health, SCV004841146.1

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

Description

This missense variant replaces isoleucine with threonine at codon 397 of the SCN5A protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in one individual affected with long QT syndrome (PMID: 19716085). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Nov 10, 2024

ClinVar

Relating variation to medicine