Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001420758 | SCV001623104 | pathogenic | Peroxisome biogenesis disorder | 2021-04-26 | criteria provided, single submitter | clinical testing | Variant summary: PEX1 c.788_789delCA (p.Thr263IlefsX6) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 249934 control chromosomes (gnomAD). c.788_789delCA has been reported in the literature in at least an individual (compound heterozygous) affected with classical Zellweger Syndrome (Walter_2001) and in another heterozygous individual (whose complete genotype was not specified) with Zellweger spectrum (Rosewich_2005). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. Fibroblasts from the patient who carried the variant of interest another pathogenic truncating variant showed no protein expression (Walter_2001). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |
Invitae | RCV001831471 | SCV004294510 | pathogenic | Zellweger spectrum disorders | 2023-02-11 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Thr263Ilefs*6) in the PEX1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PEX1 are known to be pathogenic (PMID: 9398847, 16086329, 16141001, 21031596, 26387595, 31831025). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Zellweger syndrome (PMID: 11389485). ClinVar contains an entry for this variant (Variation ID: 1098755). For these reasons, this variant has been classified as Pathogenic. |
Natera, |
RCV001831471 | SCV002079331 | pathogenic | Zellweger spectrum disorders | 2021-10-12 | no assertion criteria provided | clinical testing |