ClinVar Miner

Submissions for variant NM_000466.3(PEX1):c.1714_1715CA[1] (p.His572fs) (rs786204606)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169363 SCV000220734 likely pathogenic Peroxisome biogenesis disorder 1A (Zellweger) 2014-09-25 criteria provided, single submitter literature only
Baylor Genetics RCV001004516 SCV001163561 pathogenic Peroxisome biogenesis disorder 1A (Zellweger); Peroxisome biogenesis disorder 1B criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV001175576 SCV001339209 pathogenic Peroxisome biogenesis disorders, Zellweger syndrome spectrum 2020-03-23 criteria provided, single submitter clinical testing Variant summary: PEX1 c.1716_1717delCA (p.His572GlnfsX19) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251424 control chromosomes (gnomAD). c.1716_1717delCA has been reported in the literature in individuals affected with Zellweger Syndrome (examples- Yik_2009, Ebberink_2010). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation prior to or in 2014) cited the variant as pathogenic/likley pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV001243745 SCV001416926 pathogenic Zellweger syndrome 2019-10-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.His572Glnfs*19) in the PEX1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with peroxisomal biogenesis disorders (PMID: 19105186). ClinVar contains an entry for this variant (Variation ID: 188984). Loss-of-function variants in PEX1 are known to be pathogenic (PMID: 9398847, 16086329, 16141001, 21031596). For these reasons, this variant has been classified as Pathogenic.

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