Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001851702 | SCV002238838 | pathogenic | not provided | 2024-02-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 285 of the KCNQ4 protein (p.Gly285Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant deafness (PMID: 8035838, 10369879, 23717403). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 6244). 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 KCNQ4 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects KCNQ4 function (PMID: 20832469, 20966080). This variant disrupts the p.Gly285 amino acid residue in KCNQ4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10025409, 20966080, 25116015). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000006622 | SCV000026805 | pathogenic | Autosomal dominant nonsyndromic hearing loss 2A | 1999-02-05 | no assertion criteria provided | literature only | |
| Gene |
RCV000006622 | SCV000041117 | not provided | Autosomal dominant nonsyndromic hearing loss 2A | no assertion provided | literature only |