NM_000891.3(KCNJ2):c.199C>T (p.Arg67Trp) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Apr 20, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000170971.21

Allele description [Variation Report for NM_000891.3(KCNJ2):c.199C>T (p.Arg67Trp)]

NM_000891.3(KCNJ2):c.199C>T (p.Arg67Trp)

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.199C>T (p.Arg67Trp)

Other names:

R67W; p.R67W:CGG>TGG; p.R67W

HGVS:

NC_000017.11:g.70175238C>T
NG_008798.1:g.10704C>T
NM_000891.3:c.199C>TMANE SELECT
NP_000882.1:p.Arg67Trp
NP_000882.1:p.Arg67Trp
LRG_328t1:c.199C>T
LRG_328:g.10704C>T
NC_000017.10:g.68171379C>T
NM_000891.2:c.199C>T
P63252:p.Arg67Trp

Protein change:

ARG67TRP

Links:

UniProtKB: P63252#VAR_017851; OMIM: 600681.0006; dbSNP: rs104894580

NCBI 1000 Genomes Browser:

rs104894580

Molecular consequence:

NM_000891.3:c.199C>T - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

Decreased function

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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
SCV000223534	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Apr 20, 2022)	germline	clinical testing	Citation Link,
SCV000842588	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Jul 13, 2016)	germline	clinical testing	PubMed (14) [See all records that cite these PMIDs] 12148092, 24025405, 22806368, 15851159, 22589293, 17221872, 15911703, 12796536, 16217063, 17655675, 20713726, 24721648, 15757667, 26467025
SCV001446657	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 23, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000223534

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Apr 20, 2022)

germline

clinical testing

Citation Link,

SCV000842588

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Pathogenic
(Jul 13, 2016)

germline

clinical testing

PubMed (14)
[See all records that cite these PMIDs]

SCV001446657

Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 23, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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
not provided	germline	yes	not provided	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

KCNJ2 mutation results in Andersen syndrome with sex-specific cardiac and skeletal muscle phenotypes.

Andelfinger G, Tapper AR, Welch RC, Vanoye CG, George AL Jr, Benson DW.

Am J Hum Genet. 2002 Sep;71(3):663-8. Epub 2002 Jul 29.

PubMed [citation]

PMID:: 12148092
PMCID:: PMC379203

New exome data question the pathogenicity of genetic variants previously associated with catecholaminergic polymorphic ventricular tachycardia.

Jabbari J, Jabbari R, Nielsen MW, Holst AG, Nielsen JB, Haunsø S, Tfelt-Hansen J, Svendsen JH, Olesen MS.

Circ Cardiovasc Genet. 2013 Oct;6(5):481-9. doi: 10.1161/CIRCGENETICS.113.000118. Epub 2013 Sep 11.

PubMed [citation]

PMID:: 24025405

See all PubMed Citations (15)

Details of each submission

From GeneDx, SCV000223534.13

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Observed in multiple unrelated patients from different ethnic backgrounds with KCNJ2-related disorders referred for genetic testing at GeneDx and in published literature (Andelfinger et al., 2002; Donaldson et al., 2003; Chun et al., 2004; Davies et al., 2005; Haruna et al., 2007; Kimura et al., 2012; Tan et al., 2012; Jabbari et al., 2013; Lieve et al., 2013; Song et al., 2016); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published functional studies demonstrate the variant alters channel function (Donaldson et al., 2003; Andelfinger et al., 2002); This variant is associated with the following publications: (PMID: 11841151, 22589293, 15851159, 24561538, 23631430, 24025405, 17221872, 16217063, 22806368, 12796536, 20301441, 11861044, 27145478, 31068157, 31509255, 31567646, 23867365, 20713726, 15911703, 26582918, 32499698, 12148092)

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

From Athena Diagnostics, SCV000842588.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (14)

#	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

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001446657.1

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

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

Last Updated: Jan 19, 2025

ClinVar

Relating variation to medicine