Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000798761 | SCV000938392 | pathogenic | not provided | 2024-01-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys2278Serfs*2) 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 present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with inherited retinal disease (PMID: 36460718). ClinVar contains an entry for this variant (Variation ID: 644771). 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003230593 | SCV003928555 | likely pathogenic | Usher syndrome | 2023-04-17 | criteria provided, single submitter | clinical testing | Variant summary: CDH23 c.6831delC (p.Lys2278SerfsX2) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position are classified as pathogenic in ClinVar. The variant allele was found at a frequency of 4e-06 in 249194 control chromosomes. c.6831delC has been reported in the literature in an individual affected with Usher Syndrome (Colombo_2021). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One submitter has provided a clinical-significance assessments for this variant to ClinVar after 2014, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV003472358 | SCV004212390 | likely pathogenic | Pituitary adenoma 5, multiple types | 2021-11-08 | criteria provided, single submitter | clinical testing |