Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory of Inherited Metabolic Diseases, |
RCV002248478 | SCV002520609 | likely pathogenic | Autosomal recessive nonsyndromic hearing loss 12 | criteria provided, single submitter | clinical testing | PM1 strong, PM2 supporting, PM3 supporting, PP1 supporting, PP3 supporting | |
Baylor Genetics | RCV003475310 | SCV004210656 | likely pathogenic | Pituitary adenoma 5, multiple types | 2023-07-08 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003738165 | SCV004552948 | pathogenic | not provided | 2023-09-08 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1687042). 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. For these reasons, this variant has been classified as Pathogenic. This missense change has been observed in individual(s) with non-syndromic deafness (PMID: 35020051, 35062939, 35248088). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 269 of the CDH23 protein (p.Arg269Trp). |