ClinVar Miner

Submissions for variant NM_000466.3(PEX1):c.2368C>T (p.Arg790Ter) (rs61750417)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000780584 SCV000917980 pathogenic Peroxisome biogenesis disorders, Zellweger syndrome spectrum 2017-11-20 criteria provided, single submitter clinical testing Variant summary: The PEX1 c.2368C>T (p.Arg790X) variant results in a premature termination codon, predicted to cause a truncated or absent PEX1 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 (e.g.c.2916delA/p.Gly973fsX16, c.2992C>T/p.Arg998X). One in silico tool predicts a damaging outcome for this variant. This variant has been reported in multiple patients with Zellweger syndrome spectrum disroders. It was found in 4/245426 control chromosomes at a frequency of 0.0000163, which does not exceed the estimated maximal expected allele frequency of a pathogenic PEX1 variant (0.003873). In addition, one reputable database classified this variant as disease-causing variant. Taken together, this variant is classified as pathogenic.
Invitae RCV000798670 SCV000938296 pathogenic Peroxisome biogenesis disorder 1A (Zellweger) 2018-10-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg790*) in the PEX1 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in an individual affected with a PEX1-related condition (PMID: 12402331). 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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