ClinVar Miner

Submissions for variant NM_000466.3(PEX1):c.2T>C (p.Met1Thr)

gnomAD frequency: 0.00002  dbSNP: rs766020928
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000412294 SCV000487623 pathogenic Peroxisome biogenesis disorder 1A (Zellweger) 2016-05-27 criteria provided, single submitter clinical testing
Counsyl RCV000410262 SCV000487624 pathogenic Peroxisome biogenesis disorder 1B 2016-05-27 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001174676 SCV001337909 pathogenic Peroxisome biogenesis disorder 2020-01-10 criteria provided, single submitter clinical testing Variant summary: PEX1 c.2T>C (p.Met1?) alters the initiation codon and is predicted to result either in absence of the protein or truncation of the encoded protein due to translation initiation at a downstream codon. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 199938 control chromosomes (gnomAD). c.2T>C has been reported in the literature in multiple homozygous individuals affected with Zellweger Syndrome (ie. Ebberink_2010, Ghosh_2017). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001232745 SCV001405313 pathogenic Zellweger spectrum disorders 2024-05-30 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 present in population databases (rs766020928, gnomAD 0.01%). Disruption of the initiator codon has been observed in individuals with Zellweger spectrum disorder (PMID: 21031596, 28468868). ClinVar contains an entry for this variant (Variation ID: 371746). For these reasons, this variant has been classified as Pathogenic.
Centogene AG - the Rare Disease Company RCV001250203 SCV001424472 pathogenic Peroxisome biogenesis disorder type 1A criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005033925 SCV005669748 pathogenic Peroxisome biogenesis disorder 1A (Zellweger); Heimler syndrome 1; Peroxisome biogenesis disorder 1B 2024-06-24 criteria provided, single submitter clinical testing
Genomics England Pilot Project, Genomics England RCV000412294 SCV001760199 likely pathogenic Peroxisome biogenesis disorder 1A (Zellweger) no assertion criteria provided clinical testing
Natera, Inc. RCV001232745 SCV002079359 pathogenic Zellweger spectrum disorders 2017-03-17 no assertion criteria provided clinical testing

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