Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV002510811 | SCV002821023 | pathogenic | not provided | 2023-01-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002510811 | SCV004291792 | likely pathogenic | not provided | 2023-04-22 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects KCNQ4 function (PMID: 31995783, 34622280). 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. ClinVar contains an entry for this variant (Variation ID: 208370). This missense change has been observed in individual(s) with autosomal recessive deafness (PMID: 23717403, 31028865). It has also been observed to segregate with disease in related individuals. This variant has been reported in individual(s) with autosomal dominant deafness (PMID: 31028865); however, the role of the variant in this condition is currently unclear. This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 291 of the KCNQ4 protein (p.Pro291Leu). |
Clin |
RCV000655881 | SCV000777810 | pathogenic | Autosomal dominant nonsyndromic hearing loss 2A | 2015-08-20 | no assertion criteria provided | literature only |