ClinVar Miner

Submissions for variant NM_000466.3(PEX1):c.2922del (p.Leu974fs) (rs762324548)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478887 SCV000572331 pathogenic not provided 2017-01-16 criteria provided, single submitter clinical testing The c.2922delA variant in the PEX1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.2922delA variant causes a frameshift starting with codon Leucine 974, changes this amino acid to a Phenylalanine residue, and creates a premature Stop codon at position 15 of the new reading frame, denoted p.Leu974PhefsX15. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.2922delA variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.2922delA as a pathogenic variant.
Invitae RCV000411605 SCV001222508 pathogenic Peroxisome biogenesis disorder 1A (Zellweger) 2019-12-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu974Phefs*15) in the PEX1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs762324548, ExAC 0.001%). This variant has not been reported in the literature in individuals with PEX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 371696). 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.
Counsyl RCV000411605 SCV000487468 likely pathogenic Peroxisome biogenesis disorder 1A (Zellweger) 2015-12-22 no assertion criteria provided clinical testing
Counsyl RCV000409154 SCV000487469 likely pathogenic Deafness enamel hypoplasia nail defects 2015-12-22 no assertion criteria provided clinical testing

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