Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV002248985 | SCV002516248 | likely pathogenic | Usher syndrome type 1D | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003475309 | SCV004210652 | likely pathogenic | Pituitary adenoma 5, multiple types | 2023-07-14 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003774706 | SCV004655199 | likely pathogenic | not provided | 2023-07-13 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with CDH23-related conditions (PMID: 33095980, 33576794, 35020051). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1862 of the CDH23 protein (p.Glu1862Lys). This variant is present in population databases (rs773004408, gnomAD 0.003%). ClinVar contains an entry for this variant (Variation ID: 1685258). 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) has been performed at Invitae 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. 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. |