Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000825889 | SCV000967374 | uncertain significance | not specified | 2020-10-23 | criteria provided, single submitter | clinical testing | The p.Pro2523Leu variant in CDH23 has not been previously reported in individuals with hearing loss or Usher syndrome, but has been identified in 0.04% (14/30602) of South Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org/). This variant has been reported in ClinVar (Variation ID 667212). Computational prediction tools and conservation analysis suggest that the p.Pro2523Leu variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Pro2523Leu variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting, PP3. |
Invitae | RCV001242078 | SCV001415142 | uncertain significance | not provided | 2022-10-10 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 2523 of the CDH23 protein (p.Pro2523Leu). This variant is present in population databases (rs369761606, gnomAD 0.05%). 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: 667212). 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, |
RCV001825684 | SCV002093411 | uncertain significance | Usher syndrome type 1 | 2020-02-21 | no assertion criteria provided | clinical testing |