ClinVar Miner

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

gnomAD frequency: 0.00022  dbSNP: rs137853074
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center RCV000007896 SCV000267374 likely pathogenic Autosomal recessive nonsyndromic hearing loss 4 2016-03-18 criteria provided, single submitter reference population
Eurofins NTD LLC (GA) RCV000725885 SCV000340249 uncertain significance not provided 2016-03-24 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000358648 SCV000595305 uncertain significance not specified 2016-08-22 criteria provided, single submitter clinical testing
Invitae RCV000687427 SCV000814992 uncertain significance EAST syndrome 2021-11-19 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 348 of the KCNJ10 protein (p.Arg348Cys). This variant is present in population databases (rs137853074, gnomAD 0.2%). This missense change has been observed in individual(s) with clinical features of KCNJ10-related conditions (PMID: 19426954, 30733538; 25372295 24860705). ClinVar contains an entry for this variant (Variation ID: 7470). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change affects KCNJ10 function (PMID: 19426954). 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.
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000784954 SCV000923499 uncertain significance KCNJ10-Related Disorders 2019-01-01 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories,Mayo Clinic RCV000725885 SCV001713902 uncertain significance not provided 2019-12-16 criteria provided, single submitter clinical testing
GeneDx RCV000725885 SCV001802828 uncertain significance not provided 2021-11-09 criteria provided, single submitter clinical testing 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 individual (Zhao et al., 2014; Lin et al., 2019); Identified as heterozygous variant in an individual with enlargement of the vestibular aqueduct/Pendred syndrome; however one pathogenic variant in the SLC26A4 gene was also identified (Yang et al., 2009); Published functional studies demonstrate that R348C reduces K+ channel conductance activity (Yang et al., 2009), but the implications of these changes for the disease mechanism remain unclear; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30268946, 30733538, 31243244, 25372295, 19426954)
OMIM RCV000007896 SCV000028101 pathogenic Autosomal recessive nonsyndromic hearing loss 4 2009-05-01 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.