NM_000891.3(KCNJ2):c.899G>T (p.Gly300Val) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 1, 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:: RCV002512943.3

Allele description [Variation Report for NM_000891.3(KCNJ2):c.899G>T (p.Gly300Val)]

NM_000891.3(KCNJ2):c.899G>T (p.Gly300Val)

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.899G>T (p.Gly300Val)

Other names:

p.G300V:GGC>GTC

HGVS:

NC_000017.11:g.70175938G>T
NG_008798.1:g.11404G>T
NM_000891.3:c.899G>TMANE SELECT
NP_000882.1:p.Gly300Val
NP_000882.1:p.Gly300Val
LRG_328t1:c.899G>T
LRG_328:g.11404G>T
LRG_328p1:p.Gly300Val
NC_000017.10:g.68172079G>T
NM_000891.2:c.899G>T
P63252:p.Gly300Val

Protein change:

G300V; GLY300VAL

Links:

UniProtKB: P63252#VAR_017857; OMIM: 600681.0003; dbSNP: rs104894579

NCBI 1000 Genomes Browser:

rs104894579

Molecular consequence:

NM_000891.3:c.899G>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
SCV003442462	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 1, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 16834334, 12163457, 16419128, 17221872, 31737537, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003442462

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 1, 2022)

germline

clinical testing

PubMed (6)
[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

Andersen's syndrome mutation effects on the structure and assembly of the cytoplasmic domains of Kir2.1.

Pegan S, Arrabit C, Slesinger PA, Choe S.

Biochemistry. 2006 Jul 18;45(28):8599-606.

PubMed [citation]

PMID:: 16834334

Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome).

Tristani-Firouzi M, Jensen JL, Donaldson MR, Sansone V, Meola G, Hahn A, Bendahhou S, Kwiecinski H, Fidzianska A, Plaster N, Fu YH, Ptacek LJ, Tawil R.

J Clin Invest. 2002 Aug;110(3):381-8.

PubMed [citation]

PMID:: 12163457
PMCID:: PMC151085

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003442462.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects KCNJ2 function (PMID: 12163457, 16834334). 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) performed at Invitae indicates that this missense variant is expected to disrupt KCNJ2 protein function. ClinVar contains an entry for this variant (Variation ID: 8920). This missense change has been observed in individuals with Andersen-Tawil syndrome (PMID: 12163457, 16419128, 17221872, 31737537). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 300 of the KCNJ2 protein (p.Gly300Val).

#	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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