ClinVar Miner

Submissions for variant NM_000466.3(PEX1):c.788_789del (p.Thr263fs)

dbSNP: rs61750404
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp 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, Inc. RCV001831471 SCV002079331 pathogenic Zellweger spectrum disorders 2021-10-12 no assertion criteria provided clinical testing

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