Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001384470 | SCV001583972 | pathogenic | not provided | 2022-12-12 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1071895). This premature translational stop signal has been observed in individual(s) with Usher syndrome (PMID: 27460420). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp2811*) 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). |
| Gene |
RCV001384470 | SCV003852852 | pathogenic | not provided | 2022-10-04 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27460420) |
| Baylor Genetics | RCV003473952 | SCV004210613 | pathogenic | Pituitary adenoma 5, multiple types | 2024-03-05 | criteria provided, single submitter | clinical testing | |
| Clinical Genomics Laboratory, |
RCV003448917 | SCV004175893 | pathogenic | Usher syndrome type 1D | 2021-04-14 | no assertion criteria provided | clinical testing | The p.Trp2811* variant in the CDH23 gene has been previously reported in 1 unrelated individual with Usher syndrome, who also was reported to carry p.Asp2148Asn, a disease-associated variant in CDH23, although phase was not reported (Bonnet et al., 2016). The p.Trp2811* variant was absent from large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/). This variant leads to a premature stop codon in exon 59 of 70 coding exons, and is therefore predicted to undergo nonsense-mediated decay resulting in a truncated or absent protein. Loss of function is an established mechanism of disease for the CDH23 gene. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, there is sufficient evidence to classify the p.Trp2811* variant as pathogenic for Usher syndrome type ID in an autosomal recessive manner based on the information above. [ACMG evidence codes used: PVS1; PM3_supporting; PM2] |