Submissions for variant NM_000466.3(PEX1):c.1927del (p.Thr643fs)

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Total submissions: 3

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV002233664	SCV000827198	pathogenic	Zellweger spectrum disorders	2023-01-26	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 576112). This variant has not been reported in the literature in individuals affected with PEX1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr643Profs*2) 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).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001175577	SCV001339210	likely pathogenic	Peroxisome biogenesis disorder	2020-03-02	criteria provided, single submitter	clinical testing	Variant summary: PEX1 c.1927delA (p.Thr643ProfsX2) 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 251302 control chromosomes. To our knowledge, no occurrence of c.1927delA in individuals affected with Zellweger Syndrome and no experimental evidence demonstrating its impact on protein function have 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 likely pathogenic.
Genome-Nilou Lab	RCV000698530	SCV001810564	likely pathogenic	Peroxisome biogenesis disorder 1A (Zellweger)	2021-07-22	criteria provided, single submitter	clinical testing

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