Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000155432 | SCV000205122 | likely pathogenic | Rare genetic deafness | 2013-04-01 | criteria provided, single submitter | clinical testing | The Arg457Trp variant in CDH23 has been reported in 1/188 individuals with Usher syndrome and 2/878 control chromosomes (Le Quesne Stabej 2012). Although this variant has been seen in controls, its frequency is low enough to be consistent with a recessive carrier frequency. In addition, Computational analyses (biochem ical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) sugges t that the Arg457Trp variant may impact the protein, though this information alo ne is not predictive enough to determine pathogenicity. Furthermore, the identif ication of this variant in trans with a pathogenic CDH23 variant in two affected children in this family increases the likelihood that this variant is pathogeni c. In summary, based on the identification of this variant in two affected famil y members with a second pathogenic CDH23 variant, this variant is likely to be p athogenic. |
| Labcorp Genetics |
RCV001723725 | SCV002149679 | uncertain significance | not provided | 2023-05-08 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 178675). This missense change has been observed in individual(s) with Usher syndrome (PMID: 22135276; Invitae). This variant is present in population databases (rs727504455, gnomAD 0.002%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 457 of the CDH23 protein (p.Arg457Trp). |
| Institute of Human Genetics, |
RCV004815244 | SCV005072740 | likely pathogenic | Retinal dystrophy | 2021-01-01 | criteria provided, single submitter | clinical testing | |
| Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV001723725 | SCV001958348 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
| Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV001723725 | SCV001964453 | uncertain significance | not provided | no assertion criteria provided | clinical testing |