ClinVar Miner

Submissions for variant NM_000466.3(PEX1):c.1A>T (p.Met1Leu) (rs1057517501)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000598681 SCV000710574 pathogenic not provided 2019-01-17 criteria provided, single submitter clinical testing The c.1 A>T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.1 A>T variant is not observed in large population cohorts (Lek et al., 2016). The c.1 A>T variant alters the initiator Methionine codon, and the resultant protein would be described as p.Met1?" using a question mark to signify that it is not known if the loss of Met1 means that all protein translation is completely prevented or if an abnormal protein is produced using an alternate Met. In summary, we interpret this variant as pathogenic."
Invitae RCV001384497 SCV001584007 pathogenic Zellweger syndrome 2020-02-02 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the PEX1 mRNA. The next in-frame methionine is located at codon 209. This variant is not present in population databases (ExAC no frequency). Disruption of the initiator codon has been observed in individual(s) with Zellweger spectrum disorder (PMID: 21031596). ClinVar contains an entry for this variant (Variation ID: 371744). This variant disrupts the initiator methionine in PEX1. If translation initiates from the next in-frame methionine, the PEX1 protein would no longer include the region containing the p.Val92 amino acid residue. Other variant(s) that disrupt this residue have been observed in individuals with PEX1-related conditions (PMID: 16141001), which suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000411873 SCV000487617 likely pathogenic Peroxisome biogenesis disorder 1A (Zellweger) 2016-05-24 no assertion criteria provided clinical testing
Counsyl RCV000409502 SCV000487618 likely pathogenic Peroxisome biogenesis disorder 1B 2016-05-24 no assertion criteria provided clinical testing

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