ClinVar Miner

Submissions for variant NM_000466.3(PEX1):c.2T>C (p.Met1Thr) (rs766020928)

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Total submissions: 5
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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
Integrated Genetics/Laboratory Corporation of America RCV001174676 SCV001337909 pathogenic Peroxisome biogenesis disorders, Zellweger syndrome spectrum 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.
Invitae RCV001232745 SCV001405313 pathogenic Zellweger syndrome 2020-10-26 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, ExAC 0.01%). This variant has been observed in individual(s) 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

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