Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000156184 | SCV000205900 | uncertain significance | not specified | 2015-01-29 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The p.Ala2187Thr va riant in CDH23 has been identified by our laboratory in one Latino individual wi th hearing loss. It has been also identified in 0.03% (4/11602) of Latino chromo somes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org) . Although the variant has been identified in the general population, its freque ncy is not high enough to rule out pathogenicity. The Alanine (Ala) residue at p osition 2187 is not conserved across species, with rat and many fish species hav ing a threonine (Thr) at this position. Additional computational prediction tool s suggest that the p.Ala2187Thr variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of this variant cannot be determined with certainty; howev er based upon the conservation and computational data, we would lean towards a m ore likely benign role. |
| Invitae | RCV002515011 | SCV003454152 | uncertain significance | not provided | 2022-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2187 of the CDH23 protein (p.Ala2187Thr). This variant is present in population databases (rs727504841, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 179395). 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 CDH23 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. |
| Natera, |
RCV001826847 | SCV002090745 | uncertain significance | Usher syndrome type 1 | 2019-10-28 | no assertion criteria provided | clinical testing |