NM_002241.5(KCNJ10):c.635A>G (p.Gln212Arg) AND EAST syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 31, 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:: RCV001997474.3

Allele description [Variation Report for NM_002241.5(KCNJ10):c.635A>G (p.Gln212Arg)]

NM_002241.5(KCNJ10):c.635A>G (p.Gln212Arg)

Gene:

KCNJ10:potassium inwardly rectifying channel subfamily J member 10 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q23.2

Genomic location:

Preferred name:

NM_002241.5(KCNJ10):c.635A>G (p.Gln212Arg)

HGVS:

NC_000001.11:g.160041898T>C
NG_016411.1:g.33274A>G
NM_002241.5:c.635A>GMANE SELECT
NP_002232.2:p.Gln212Arg
NC_000001.10:g.160011688T>C

Protein change:

Q212R

Links:

dbSNP: rs36040296

NCBI 1000 Genomes Browser:

rs36040296

Molecular consequence:

NM_002241.5:c.635A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: EAST syndrome (SESAMES)
Synonyms:: SeSAME syndrome; Seizures, sensorineural deafness, ataxia, mental retardation and electrolyte imbalance; Epilepsy, ataxia, sensorineural deafness and tubulopathy; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0013005; MedGen: C2748572; Orphanet: 199343; OMIM: 612780

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
SCV002232878	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 31, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26867573, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002232878

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 31, 2022)

germline

clinical testing

PubMed (2)
[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

Novel KCNJ10 Gene Variations Compromise Function of Inwardly Rectifying Potassium Channel 4.1.

Méndez-González MP, Kucheryavykh YV, Zayas-Santiago A, Vélez-Carrasco W, Maldonado-Martínez G, Cubano LA, Nichols CG, Skatchkov SN, Eaton MJ.

J Biol Chem. 2016 Apr 1;291(14):7716-26. doi: 10.1074/jbc.M115.679910. Epub 2016 Feb 11.

PubMed [citation]

PMID:: 26867573
PMCID:: PMC4817196

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002232878.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

ClinVar contains an entry for this variant (Variation ID: 1449295). This variant has not been reported in the literature in individuals affected with KCNJ10-related conditions. This variant is present in population databases (rs36040296, gnomAD 0.002%). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 212 of the KCNJ10 protein (p.Gln212Arg). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. Experimental studies have shown that this missense change affects KCNJ10 function (PMID: 26867573).

#	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: Apr 6, 2024

ClinVar

Relating variation to medicine