Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001844718 | SCV002103962 | uncertain significance | not specified | 2022-02-18 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002034736 | SCV002219265 | likely pathogenic | not provided | 2024-08-26 | criteria provided, single submitter | clinical testing | This sequence change affects codon 1615 of the CDH23 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the CDH23 protein. This variant also falls at the last nucleotide of exon 38, which is part of the consensus splice site for this exon. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has been observed in individual(s) with Usher syndrome (external communication). 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: 1343701). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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. |