Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000669146 | SCV000793863 | likely pathogenic | Peroxisome biogenesis disorder type 3B; Peroxisome biogenesis disorder 3A (Zellweger) | 2017-09-01 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003653255 | SCV004376681 | pathogenic | Peroxisome biogenesis disorder 3A (Zellweger) | 2023-04-25 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu258Cysfs*19) in the PEX12 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 102 amino acid(s) of the PEX12 protein. This variant has not been reported in the literature in individuals affected with PEX12-related conditions. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the PEX12 protein in which other variant(s) (p.Gln349del) have been determined to be pathogenic (PMID: 15542397, 21031596; 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 553650). |