Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003077268 | SCV003454820 | uncertain significance | not provided | 2024-02-23 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 2178 of the CDH23 protein (p.Ile2178Phe). This variant is present in population databases (rs766571386, gnomAD 0.005%). 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: 2147593). 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 with a negative predictive value of 95%. 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. |
| Laboratory of Prof. |
RCV004821331 | SCV005442579 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 12 | 2024-12-25 | criteria provided, single submitter | research | The CDH23 c.6532A>T:p.(Ile2178Phe) variant is extremely rare and possibly deleterious. It was detected in an individual with sloping normal-to-severe HL that carried an additional pathogenic variant in another USH gene, MYO7A, c.1801G>A:p.(Ala601Thr), suggesting digenic inheritance. This patient has Meniere's disease, which has been associated with digenic inheritance involving MYO7A and other USH genes, including CDH23 (PMID: 34391192). |