ClinVar Miner

Submissions for variant NM_002241.5(KCNJ10):c.541T>C (p.Phe181Leu)

gnomAD frequency: 0.00002  dbSNP: rs374746230
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001345104 SCV001539203 uncertain significance EAST syndrome 2022-02-03 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 181 of the KCNJ10 protein (p.Phe181Leu). This variant is present in population databases (rs374746230, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with KCNJ10-related conditions. ClinVar contains an entry for this variant (Variation ID: 1041315). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KCNJ10 protein function. 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.
Ambry Genetics RCV002350634 SCV002649356 uncertain significance Inborn genetic diseases 2018-01-31 criteria provided, single submitter clinical testing The p.F181L variant (also known as c.541T>C), located in coding exon 1 of the KCNJ10 gene, results from a T to C substitution at nucleotide position 541. The phenylalanine at codon 181 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is conflicting at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002493770 SCV002783452 uncertain significance Autosomal recessive nonsyndromic hearing loss 4; Pendred syndrome; EAST syndrome 2022-03-23 criteria provided, single submitter clinical testing

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.