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NM_002241.5(KCNJ10):c.1042C>T (p.Arg348Cys)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(1);Uncertain significance(5)

Review status:
criteria provided, conflicting interpretations
Submissions:
8 (Most recent: Aug 20, 2021)
Last evaluated:
Oct 1, 2020
Accession:
VCV000007470.8
Variation ID:
7470
Description:
single nucleotide variant
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NM_002241.5(KCNJ10):c.1042C>T (p.Arg348Cys)

Allele ID
22509
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
1q23.2
Genomic location
1: 160041491 (GRCh38) GRCh38 UCSC
1: 160011281 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000001.10:g.160011281G>A
NC_000001.11:g.160041491G>A
NG_016411.1:g.33681C>T
NM_002241.5:c.1042C>T MANE Select NP_002232.2:p.Arg348Cys missense
Protein change
R348C
Other names
-
Canonical SPDI
NC_000001.11:160041490:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
0.00060 (A)

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00022
The Genome Aggregation Database (gnomAD), exomes 0.00018
1000 Genomes Project 0.00060
Trans-Omics for Precision Medicine (TOPMed) 0.00035
Exome Aggregation Consortium (ExAC) 0.00024
Links
ClinGen: CA254188
OMIM: 602208.0009
dbSNP: rs137853074
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 3 criteria provided, multiple submitters, no conflicts Dec 16, 2019 RCV000725885.3
Likely pathogenic 2 criteria provided, single submitter Mar 18, 2016 RCV000007896.5
Uncertain significance 1 criteria provided, single submitter Aug 22, 2016 RCV000358648.2
Uncertain significance 1 criteria provided, single submitter Oct 1, 2020 RCV000687427.4
Uncertain significance 1 criteria provided, single submitter Jan 1, 2019 RCV000784954.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
KCNJ10 - - GRCh38
GRCh37
269 284

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Jan 01, 2019)
criteria provided, single submitter
Method: clinical testing
KCNJ10-Related Disorders
Allele origin: unknown
Genomic Research Center,Shahid Beheshti University of Medical Sciences
Accession: SCV000923499.1
Submitted: (Apr 08, 2019)
Evidence details
Uncertain significance
(Oct 01, 2020)
criteria provided, single submitter
Method: clinical testing
EAST syndrome
Allele origin: germline
Invitae
Accession: SCV000814992.4
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (3)
Comment:
This sequence change replaces arginine with cysteine at codon 348 of the KCNJ10 protein (p.Arg348Cys). The arginine residue is moderately conserved and there is a … (more)
Likely pathogenic
(Mar 18, 2016)
criteria provided, single submitter
Method: reference population
Deafness, autosomal recessive 4, with enlarged vestibular aqueduct
Allele origin: germline
Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center
Accession: SCV000267374.1
Submitted: (Apr 14, 2016)
Evidence details
Publications
PubMed (1)
Uncertain significance
(Aug 22, 2016)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Genetic Services Laboratory, University of Chicago
Accession: SCV000595305.1
Submitted: (Jul 05, 2017)
Evidence details
Uncertain significance
(Mar 24, 2016)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000340249.4
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/emvc…
Uncertain significance
(Dec 16, 2019)
criteria provided, single submitter
Method: clinical testing
Not provided
Allele origin: germline
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001713902.1
Submitted: (May 26, 2021)
Evidence details
Pathogenic
(May 01, 2009)
no assertion criteria provided
Method: literature only
DEAFNESS, AUTOSOMAL RECESSIVE 4, WITH ENLARGED VESTIBULAR AQUEDUCT, DIGENIC
Allele origin: germline
OMIM
Accession: SCV000028101.3
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (1)
Uncertain significance
(Apr 08, 2020)
no assertion criteria provided
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001802828.1
Submitted: (Aug 20, 2021)
Evidence details
Comment:
Identified as heterozygous variant in individuals with enlargement of the vestibular aqueduct; however, biallelic pathogenic variants in the SLC26A4 gene were also identified in each … (more)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Elucidation of the unique mutation spectrum of severe hearing loss in a Vietnamese pediatric population. Han JJ Scientific reports 2019 PMID: 30733538
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Mutations of KCNJ10 together with mutations of SLC26A4 cause digenic nonsyndromic hearing loss associated with enlarged vestibular aqueduct syndrome. Yang T American journal of human genetics 2009 PMID: 19426954
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=KCNJ10 - - - -

Text-mined citations for rs137853074...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 07, 2021