NM_000891.3(KCNJ2):c.973C>T (p.Arg325Cys) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 28, 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:: RCV000816436.8

Allele description [Variation Report for NM_000891.3(KCNJ2):c.973C>T (p.Arg325Cys)]

NM_000891.3(KCNJ2):c.973C>T (p.Arg325Cys)

Gene:

KCNJ2:potassium inwardly rectifying channel subfamily J member 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q24.3

Genomic location:

Preferred name:

NM_000891.3(KCNJ2):c.973C>T (p.Arg325Cys)

Other names:

p.R325C:CGC>TGC

HGVS:

NC_000017.11:g.70176012C>T
NG_008798.1:g.11478C>T
NM_000891.3:c.973C>TMANE SELECT
NP_000882.1:p.Arg325Cys
NP_000882.1:p.Arg325Cys
LRG_328t1:c.973C>T
LRG_328:g.11478C>T
LRG_328p1:p.Arg325Cys
NC_000017.10:g.68172153C>T
NM_000891.2:c.973C>T

Protein change:

R325C

Links:

dbSNP: rs202067116

NCBI 1000 Genomes Browser:

rs202067116

Molecular consequence:

NM_000891.3:c.973C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Andersen Tawil syndrome (LQT7)
Synonyms:: Andersen Syndrome; Andersen cardiodysrhythmic periodic paralysis; Long QT syndrome 7; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008222; MedGen: C1563715; Orphanet: 37553; OMIM: 170390

Name:: Short QT syndrome type 3
Identifiers:: MONDO: MONDO:0012314; MedGen: C1865018; Orphanet: 51083; OMIM: 609622

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000956945	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 28, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 27920829, 30975432, 31737537, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000956945

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 28, 2023)

germline

clinical testing

PubMed (4)
[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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical and genetic features of Australian families with long QT syndrome: A registry-based study.

Burns C, Ingles J, Davis AM, Connell V, Gray B, Hunt L, McGaughran J, Semsarian C.

J Arrhythm. 2016 Dec;32(6):456-461. Epub 2016 Mar 15.

PubMed [citation]

PMID:: 27920829
PMCID:: PMC5129121

Usefulness of Genetic Testing in Sudden Cardiac Arrest Survivors With or Without Previous Clinical Evidence of Heart Disease.

Asatryan B, Schaller A, Seiler J, Servatius H, Noti F, Baldinger SH, Tanner H, Roten L, Dillier R, Lam A, Haeberlin A, Conte G, Saguner AM, Müller SA, Duru F, Auricchio A, Ammann P, Sticherling C, Burri H, Reichlin T, Wilhelm M, Medeiros-Domingo A.

Am J Cardiol. 2019 Jun 15;123(12):2031-2038. doi: 10.1016/j.amjcard.2019.02.061. Epub 2019 Mar 18.

PubMed [citation]

PMID:: 30975432

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000956945.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 325 of the KCNJ2 protein (p.Arg325Cys). This variant is present in population databases (rs202067116, gnomAD 0.02%). This missense change has been observed in individual(s) with arrhythmogenic disorders and/or long QT syndrome (PMID: 27920829, 30975432, 31737537). ClinVar contains an entry for this variant (Variation ID: 190821). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on KCNJ2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been 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	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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