Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000214408 | SCV000271347 | pathogenic | Rare genetic deafness | 2015-07-30 | criteria provided, single submitter | clinical testing | The p.Arg3186X variant in CDH23 has not been previously reported in individuals with hearing loss or Usher syndrome and was absent from large population studies . This nonsense variant leads to a premature termination codon at position 3186, which is predicted to lead to a truncated or absent protein. Loss of function o f the CDH23 gene is an established disease mechanism in autosomal recessive Ushe r syndrome type 1D. In summary, this variant meets our criteria to be classified as pathogenic for Usher syndrome based on the predicted impact of the variant. |
| Invitae | RCV002517526 | SCV003483268 | pathogenic | not provided | 2023-12-02 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg3186*) in the CDH23 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CDH23 are known to be pathogenic (PMID: 11138009, 21940737). 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 variant has not been reported in the literature in individuals affected with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 228330). For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV003474995 | SCV004210597 | likely pathogenic | Pituitary adenoma 5, multiple types | 2023-10-16 | criteria provided, single submitter | clinical testing |