Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000410459 | SCV000485867 | likely pathogenic | Usher syndrome type 1F | 2016-02-22 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003679000 | SCV004422905 | pathogenic | not provided | 2023-03-21 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the PCDH15 protein in which other variant(s) (p.Val1578Alafs*6) have been determined to be pathogenic (PMID: 33089500; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 370524). This variant has not been reported in the literature in individuals affected with PCDH15-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 32 of the PCDH15 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. |