Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000671485 | SCV000796462 | uncertain significance | Usher syndrome type 1F | 2017-12-14 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003767994 | SCV004653868 | pathogenic | not provided | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser1523Thrfs*2) in the PCDH15 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 433 amino acid(s) of the PCDH15 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PCDH15-related conditions. ClinVar contains an entry for this variant (Variation ID: 555627). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. For these reasons, this variant has been classified as Pathogenic. |