Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001202418 | SCV001373529 | uncertain significance | EAST syndrome | 2024-06-12 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 81 of the KCNJ10 protein (p.Leu81Phe). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 934084). 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 not expected to disrupt KCNJ10 protein function with a negative predictive value of 80%. 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 | RCV002451416 | SCV002737379 | uncertain significance | Inborn genetic diseases | 2019-04-25 | criteria provided, single submitter | clinical testing | The p.L81F variant (also known as c.241C>T), located in coding exon 1 of the KCNJ10 gene, results from a C to T substitution at nucleotide position 241. The leucine at codon 81 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly conserved through mammals. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV002480661 | SCV002775834 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 4; Pendred syndrome; EAST syndrome | 2021-10-28 | criteria provided, single submitter | clinical testing |