ClinVar Miner

Submissions for variant NM_000466.3(PEX1):c.1897C>T (p.Arg633Ter) (rs61750409)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665705 SCV000789869 likely pathogenic Peroxisome biogenesis disorder 1A (Zellweger) 2017-02-24 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV001193608 SCV001362556 likely pathogenic Peroxisome biogenesis disorders, Zellweger syndrome spectrum 2019-07-19 criteria provided, single submitter clinical testing Variant summary: PEX1 c.1897C>T (p.Arg633X) 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 (eg. c.2368C>T;p.Arg790X, c.2916delA; p.Gly973fsX16). The variant allele was found at a frequency of 4e-06 in 251234 control chromosomes (gnomAD) and been reported in the literature in individuals affected with Peroxisome Biogenesis Disorders such as Zellweger spectrum disorder and neonatal adrenoleucodystrophy (Rosewich_2005, Tamura_2001). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect (Tamura_2001). 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 likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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