Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV003474483 | SCV004210602 | likely pathogenic | Pituitary adenoma 5, multiple types | 2023-10-11 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003738475 | SCV004561134 | likely pathogenic | not provided | 2023-11-13 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1845 of the CDH23 protein (p.Asn1845Ser). This variant is present in population databases (no rsID available, gnomAD 0.004%). This missense change has been observed in individual(s) with deafness (PMID: 36468022). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. 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. This variant disrupts the p.Asn1845 amino acid residue in CDH23. Other variant(s) that disrupt this residue have been observed in individuals with CDH23-related conditions (PMID: 35651951), which suggests that this may be a clinically significant amino acid residue. 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. |