Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000603092 | SCV000731515 | pathogenic | Rare genetic deafness | 2017-03-31 | criteria provided, single submitter | clinical testing | The c.8064+1G>T variant in CDH23 has not been previously reported in individuals with hearing loss or Usher syndrome, or in large population studies. This varia nt occurs in the invariant region (+/- 1,2) of the splice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent protein . Loss of CDH23 function is an established mechanism of Usher syndrome. In summa ry, this variant meets criteria to be classified as pathogenic for Usher syndrom e in an autosomal recessive manner based on its predicted impact on the protein and extremely low frequency in the general population. |
| Labcorp Genetics |
RCV001222595 | SCV001394702 | pathogenic | not provided | 2023-10-03 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 56 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 (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with Usher syndrome (PMID: 35020051). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 517297). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV004568332 | SCV005060182 | likely pathogenic | Pituitary adenoma 5, multiple types | 2024-01-04 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001222595 | SCV005327443 | likely pathogenic | not provided | 2023-09-10 | criteria provided, single submitter | clinical testing | Canonical splice site variant predicted to result in an in-frame loss of the adjacent exon in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 11138009) |