Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000221407 | SCV000271346 | pathogenic | Rare genetic deafness | 2015-02-26 | criteria provided, single submitter | clinical testing | The c.7483-1G>C variant in CDH23 has not been previously reported in individuals with hearing loss or in large population studies. This variant occurs in the in variant region (+/- 1,2) of the splice consensus sequence and is predicted to ca use altered splicing leading to an abnormal or absent protein. In summary, this variant meets our criteria to be classified as pathogenic for Usher syndrome in an autosomal recessive manner (http://www.partners.org/personalizedmedicine/LMM) based upon its predicted impact on the protein and low frequency in the general population. |
| Labcorp Genetics |
RCV001853426 | SCV002309904 | likely pathogenic | not provided | 2021-08-23 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 53 of the CDH23 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CDH23 are known to be pathogenic (PMID: 11138009, 21940737). This variant is not present in population databases (ExAC 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: 228329). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |