Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Kariminejad - |
RCV001814384 | SCV001755223 | likely pathogenic | Ear malformation | 2021-07-10 | criteria provided, single submitter | clinical testing | |
Center For Human Genetics And Laboratory Diagnostics, |
RCV002071934 | SCV002320728 | likely pathogenic | Autosomal recessive nonsyndromic hearing loss 12 | 2022-03-14 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV005094750 | SCV005821730 | uncertain significance | not provided | 2025-01-18 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 956 of the CDH23 protein (p.Glu956Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with deafness (PMID: 38374194; internal data). ClinVar contains an entry for this variant (Variation ID: 1180655). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CDH23 protein function. This variant disrupts the p.Glu956 amino acid residue in CDH23. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22899989, 25963016). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |