NM_000891.3(KCNJ2):c.212A>T (p.Asp71Val) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 19, 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:: RCV001851763.3

Allele description [Variation Report for NM_000891.3(KCNJ2):c.212A>T (p.Asp71Val)]

NM_000891.3(KCNJ2):c.212A>T (p.Asp71Val)

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.212A>T (p.Asp71Val)

HGVS:

NC_000017.11:g.70175251A>T
NG_008798.1:g.10717A>T
NM_000891.3:c.212A>TMANE SELECT
NP_000882.1:p.Asp71Val
NP_000882.1:p.Asp71Val
LRG_328t1:c.212A>T
LRG_328:g.10717A>T
LRG_328p1:p.Asp71Val
NC_000017.10:g.68171392A>T
NM_000891.2:c.212A>T
P63252:p.Asp71Val

Protein change:

D71V; ASP71VAL

Links:

UniProtKB: P63252#VAR_017852; OMIM: 600681.0001; dbSNP: rs104894575

NCBI 1000 Genomes Browser:

rs104894575

Molecular consequence:

NM_000891.3:c.212A>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
SCV002240582	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 19, 2022)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 11371347, 24861851, 12163457, 12909315, 14522976, 22002906, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002240582

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 19, 2022)

germline

clinical testing

PubMed (7)
[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

Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome.

Plaster NM, Tawil R, Tristani-Firouzi M, Canún S, Bendahhou S, Tsunoda A, Donaldson MR, Iannaccone ST, Brunt E, Barohn R, Clark J, Deymeer F, George AL Jr, Fish FA, Hahn A, Nitu A, Ozdemir C, Serdaroglu P, Subramony SH, Wolfe G, Fu YH, Ptácek LJ.

Cell. 2001 May 18;105(4):511-9.

PubMed [citation]

PMID:: 11371347

Andersen-Tawil syndrome: report of 3 novel mutations and high risk of symptomatic cardiac involvement.

Kostera-Pruszczyk A, Potulska-Chromik A, Pruszczyk P, Bieganowska K, Miszczak-Knecht M, Bienias P, Szczałuba K, Lee HY, Quinn E, Ploski R, Kaminska A, Ptáček LJ.

Muscle Nerve. 2015 Feb;51(2):192-6. doi: 10.1002/mus.24293. Epub 2014 Nov 19.

PubMed [citation]

PMID:: 24861851

See all PubMed Citations (7)

Details of each submission

From Invitae, SCV002240582.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This missense change has been observed in individuals with Andersen-Tawil syndrome (PMID: 11371347, 24861851). It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects KCNJ2 function (PMID: 12163457, 12909315, 14522976, 22002906). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 8918). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 71 of the KCNJ2 protein (p.Asp71Val).

#	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: Feb 28, 2024

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