NM_000335.5(SCN5A):c.5689C>T (p.Arg1897Cys) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 23, 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:: RCV000619017.12

Allele description [Variation Report for NM_000335.5(SCN5A):c.5689C>T (p.Arg1897Cys)]

NM_000335.5(SCN5A):c.5689C>T (p.Arg1897Cys)

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.5689C>T (p.Arg1897Cys)

HGVS:

NC_000003.12:g.38550680G>A
NG_008934.1:g.103993C>T
NM_000335.5:c.5689C>TMANE SELECT
NM_001099404.2:c.5692C>T
NM_001099405.2:c.5638C>T
NM_001160160.2:c.5593C>T
NM_001160161.2:c.5530C>T
NM_001354701.2:c.5635C>T
NM_198056.3:c.5692C>T
NP_000326.2:p.Arg1897Cys
NP_001092874.1:p.Arg1898Cys
NP_001092875.1:p.Arg1880Cys
NP_001153632.1:p.Arg1865Cys
NP_001153633.1:p.Arg1844Cys
NP_001341630.1:p.Arg1879Cys
NP_932173.1:p.Arg1898Cys
NP_932173.1:p.Arg1898Cys
LRG_289t1:c.5692C>T
LRG_289:g.103993C>T
LRG_289p1:p.Arg1898Cys
NC_000003.11:g.38592171G>A
NM_198056.2:c.5692C>T

Protein change:

R1844C

Links:

dbSNP: rs373118001

NCBI 1000 Genomes Browser:

rs373118001

Molecular consequence:

NM_000335.5:c.5689C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.5692C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.5638C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.5593C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.5530C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.5635C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.5692C>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

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000736116	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Mar 23, 2023)	germline	clinical testing	PubMed (11) [See all records that cite these PMIDs] 25904541, 26173111, 26746457, 27707468, 29306897, 29447731, 30847666, 32533946, 32880476, 34426522, 34621001 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000736116

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Mar 23, 2023)

germline

clinical testing

PubMed (11)
[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

Enhanced Classification of Brugada Syndrome-Associated and Long-QT Syndrome-Associated Genetic Variants in the SCN5A-Encoded Na(v)1.5 Cardiac Sodium Channel.

Kapplinger JD, Giudicessi JR, Ye D, Tester DJ, Callis TE, Valdivia CR, Makielski JC, Wilde AA, Ackerman MJ.

Circ Cardiovasc Genet. 2015 Aug;8(4):582-95. doi: 10.1161/CIRCGENETICS.114.000831. Epub 2015 Apr 22.

PubMed [citation]

PMID:: 25904541
PMCID:: PMC4878676

Comprehensive Genetic Characterization of a Spanish Brugada Syndrome Cohort.

Selga E, Campuzano O, Pinsach-Abuin ML, Pérez-Serra A, Mademont-Soler I, Riuró H, Picó F, Coll M, Iglesias A, Pagans S, Sarquella-Brugada G, Berne P, Benito B, Brugada J, Porres JM, López Zea M, Castro-Urda V, Fernández-Lozano I, Brugada R.

PLoS One. 2015;10(7):e0132888. doi: 10.1371/journal.pone.0132888.

PubMed [citation]

PMID:: 26173111
PMCID:: PMC4501715

See all PubMed Citations (11)

Details of each submission

From Ambry Genetics, SCV000736116.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (11)

Description

The p.R1898C variant (also known as c.5692C>T), located in coding exon 27 of the SCN5A gene, results from a C to T substitution at nucleotide position 5692. The arginine at codon 1898 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported in Brugada syndrome and sudden unexplained nocturnal death cohorts; however, clinical details were limited and the sudden death case also had a second SCN5A variant detected (Selga E et al. PLoS ONE, 2015 Jul;10:e0132888; Zhang L et al. Mayo Clin. Proc., 2016 Nov;91:1503-1514). This variant has also been detected in individuals reported to have dilated cardiomyopathy or noncompaction cardiomyopathy; however, clinical details were limited and some reports may overlap (van Waning JI et al. J Am Coll Cardiol. 2018 Feb;71(7):711-722; van Lint FHM et al. Neth Heart J. 2019 Jun;27(6):304-309; Verdonschot JAJ et al. Circ Genom Precis Med. 2020 Oct;13(5):476-487). In addition, this variant has been detected in cohorts not selected for the presence of cardiovascular disease; however, details were limited (Chetruengchai W et al. J Hum Genet. 2022 Mar;67(3):137-142; Kars ME et al. Proc Natl Acad Sci U S A. 2021 Sep;118(36)). Functional studies suggest this variant may result in reduced ion channel current; however, additional evidence is needed to confirm this finding (Glazer AM et al. Am J Hum Genet. 2020 Jul;107(1):111-123).This amino acid position is highly conserved in available 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: Oct 26, 2024

ClinVar

Relating variation to medicine