Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001956332 | SCV002243773 | pathogenic | not provided | 2024-01-02 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 30 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 individuals with Usher syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 1458365). 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. |
| Laboratorio de Genetica e Diagnostico Molecular, |
RCV003136378 | SCV003807183 | likely pathogenic | Autosomal recessive nonsyndromic hearing loss 12 | 2022-07-06 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PVS1 strong, PM2 moderated |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003230720 | SCV003928556 | likely pathogenic | Usher syndrome | 2023-04-05 | criteria provided, single submitter | clinical testing | Variant summary: CDH23 c.3579+2T>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a canonical 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 243350 control chromosomes (gnomAD). To our knowledge, no occurrence of c.3579+2T>C in individuals affected with Usher Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters have assessed the variant since 2014: one classified the variant as likely pathogenic and one as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV003475245 | SCV004212356 | likely pathogenic | Pituitary adenoma 5, multiple types | 2022-09-22 | criteria provided, single submitter | clinical testing |