Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000604670 | SCV000731544 | pathogenic | Rare genetic deafness | 2017-04-25 | criteria provided, single submitter | clinical testing | The p.Pro3059fs variant in CDH23 has not been previously reported in individuals with hearing loss or Usher syndrome and was absent from in large population stu dies. This variant is predicted to cause a frameshift, which alters the protein? s amino acid sequence beginning at position 3059 and leads to a premature termin ation codon 28 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the CDH23 ge ne is an established disease mechanism in individuals with Usher syndrome. In su mmary, this variant meets criteria to be classified as pathogenic for hearing lo ss in an autosomal recessive manner. |
| Invitae | RCV001855250 | SCV002219221 | pathogenic | not provided | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Pro3059Argfs*28) 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). This variant is not present in population databases (gnomAD no frequency). 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: 517317). For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV003471975 | SCV004210600 | likely pathogenic | Pituitary adenoma 5, multiple types | 2023-10-12 | criteria provided, single submitter | clinical testing |