ClinVar Miner

Submissions for variant NM_000466.3(PEX1):c.2387_2388TC[2] (p.Arg798fs) (rs61750414)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169203 SCV000220453 likely pathogenic Peroxisome biogenesis disorder 1A (Zellweger) 2014-06-25 criteria provided, single submitter literature only
Invitae RCV000169203 SCV001232225 pathogenic Peroxisome biogenesis disorder 1A (Zellweger) 2019-05-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg798Serfs*35) in the PEX1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs61750414, ExAC 0.02%). This variant has been observed in an individual affected with Zellweger syndrome (PMID: 16088892). ClinVar contains an entry for this variant (Variation ID: 188851). 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.
Integrated Genetics/Laboratory Corporation of America RCV001201267 SCV001372377 pathogenic Peroxisome biogenesis disorders, Zellweger syndrome spectrum 2020-06-16 criteria provided, single submitter clinical testing Variant summary: PEX1 c.2391_2392delTC (p.Arg798SerfsX35) 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 allele was found at a frequency of 8e-06 in 251226 control chromosomes. c.2391_2392delTC has been reported in the literature in at-least one individual affected with Zellweger Syndrome and has been subsequently cited by others (example, Maxwell_2005, Crane_2005, Ebberink_2011). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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