ClinVar Miner

Submissions for variant NM_000466.3(PEX1):c.1842del (p.Glu615fs)

dbSNP: rs267608176
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410765 SCV000487496 likely pathogenic Peroxisome biogenesis disorder 1A (Zellweger) 2016-01-26 criteria provided, single submitter clinical testing
Counsyl RCV000412291 SCV000487497 likely pathogenic Peroxisome biogenesis disorder 1B 2016-01-26 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001194280 SCV001363679 pathogenic Peroxisome biogenesis disorder 2019-10-25 criteria provided, single submitter clinical testing Variant summary: PEX1 c.1842delA (p.Glu615LysfsX30) 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 allele was found at a frequency of 1.6e-05 in 251282 control chromosomes. c.1842delA has been reported in the literature in individuals affected with biochemically confirmed diagnosis of Zellweger Syndrome (Yik_2009, Ebberink_2010). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has 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 likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV001833495 SCV002175156 pathogenic Zellweger spectrum disorders 2023-12-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu615Lysfs*30) 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: 21031596, 26387595, 31831025). This variant is present in population databases (rs267608176, gnomAD 0.009%). This premature translational stop signal has been observed in individual(s) with clinical features of Zellweger spectrum disorder (PMID: 19105186, 21031596). This variant is also known as c.1840delA. ClinVar contains an entry for this variant (Variation ID: 371703). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Preventiongenetics, part of Exact Sciences RCV003418087 SCV004117987 pathogenic PEX1-related condition 2023-08-10 criteria provided, single submitter clinical testing The PEX1 c.1842delA variant is predicted to result in a frameshift and premature protein termination (p.Glu615Lysfs*30). This variant has been reported in individuals with clinical features of PEX1-related disorders (Reported as c.1840delA in Yik et al 2009. PubMed ID: 19105186; Yépez VA et al 2022. PubMed ID: 35379322). This variant is reported in 0.0087% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/7-92135619-CT-C). Frameshift variants in PEX1 are expected to be pathogenic. This variant is interpreted as pathogenic.
Natera, Inc. RCV001833495 SCV002076887 pathogenic Zellweger spectrum disorders 2020-03-26 no assertion criteria provided clinical testing

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