Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001870863 | SCV002127861 | pathogenic | Peroxisome biogenesis disorder | 2024-01-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Pro472Glnfs*8) in the PEX6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PEX6 are known to be pathogenic (PMID: 10408779, 21031596, 31831025). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PEX6-related conditions. ClinVar contains an entry for this variant (Variation ID: 1369876). For these reasons, this variant has been classified as Pathogenic. |
| Neuberg Centre For Genomic Medicine, |
RCV003339778 | SCV004048122 | likely pathogenic | Peroxisome biogenesis disorder 4A (Zellweger) | criteria provided, single submitter | clinical testing | The frameshift deletion p.P472Qfs*8 in PEX6 (NM_000287.4) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.P472Qfs*8 variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant is predicted to cause loss of normal protein function through protein truncation caused a frameshift mutation. The frame shifted sequence continues 8 residues until a stop codon is reached. The p.P472Qfs*8 variant is a loss of function variant in the gene PEX6, which is intolerant of Loss of Function variants. For these reasons, this variant has been classified as Likely Pathogenic. The observed variant was not detected in the spouse. | |
| Baylor Genetics | RCV003475132 | SCV004201597 | likely pathogenic | Heimler syndrome 2 | 2022-12-16 | criteria provided, single submitter | clinical testing |