NM_002241.5(KCNJ10):c.1043G>A (p.Arg348His) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 30, 2021
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:: RCV003224208.8

Allele description [Variation Report for NM_002241.5(KCNJ10):c.1043G>A (p.Arg348His)]

NM_002241.5(KCNJ10):c.1043G>A (p.Arg348His)

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.1043G>A (p.Arg348His)

Other names:

p.R348H:CGC>CAC

HGVS:

NC_000001.11:g.160041490C>T
NG_016411.1:g.33682G>A
NM_002241.5:c.1043G>AMANE SELECT
NP_002232.2:p.Arg348His
NC_000001.10:g.160011280C>T
NM_002241.4:c.1043G>A

Protein change:

R348H

Links:

dbSNP: rs146396982

NCBI 1000 Genomes Browser:

rs146396982

Molecular consequence:

NM_002241.5:c.1043G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Autosomal recessive nonsyndromic hearing loss 4 (DFNB4)
Synonyms:: NEUROSENSORY NONSYNDROMIC RECESSIVE DEAFNESS 4; DEAFNESS, AUTOSOMAL RECESSIVE 4, WITH ENLARGED VESTIBULAR AQUEDUCT, DIGENIC; Nonsyndromic enlarged vestibular aqueduct (NSEVA); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010933; MedGen: C3538946; Orphanet: 90636; OMIM: 600791

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
SCV003920098	Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 30, 2021)	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

SCV003920098

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 30, 2021)

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV003920098.1

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

Description

KCNJ10 NM_002241.4 exon 2 p.Arg348His (c.1043G>A): This variant has been reported in the literature in 1 individual with congenital hyperinsulinism of infancy (CHI) (Proverbio 2013 PMID:23869231), as well as in 1 individual with autism and epilepsy, segregating with disease in 1 affected relative (Sicca 2016 PMID:7677466). This variant is present in 83/126554 European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs146396982). This variant is present in ClinVar (Variation ID:205823). Evolutionary conservation and computational predictive tools for this variant are unclear. Zebrafish and patch-clamp functional studies suggest a deleterious effect of this variant; however, further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

#	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: Oct 26, 2024

ClinVar

Relating variation to medicine