ClinVar Miner

Submissions for variant NM_000466.3(PEX1):c.643_647del (p.Thr215fs)

dbSNP: rs786204544
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169257 SCV000220546 likely pathogenic Peroxisome biogenesis disorder 1A (Zellweger) 2014-07-24 criteria provided, single submitter literature only
Invitae RCV001850395 SCV002179793 pathogenic Zellweger spectrum disorders 2022-04-06 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 188897). This premature translational stop signal has been observed in individual(s) with PEX1-related conditions (PMID: 19105186). This variant is present in population databases (rs786204544, gnomAD 0.06%). This sequence change creates a premature translational stop signal (p.Thr215Alafs*11) 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: 9398847, 16086329, 16141001, 21031596, 26387595, 31831025).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002271442 SCV002555669 pathogenic Peroxisome biogenesis disorder 2022-06-06 criteria provided, single submitter clinical testing Variant summary: PEX1 c.643_647delACCAA (p.Thr215AlafsX11) 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 5.3e-06 in 190114 control chromosomes. c.643_647delACCAA has been reported in the literature in at least one individual affected with Zellweger Syndrome. 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 pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics RCV003474902 SCV004203367 pathogenic Heimler syndrome 1 2023-02-21 criteria provided, single submitter clinical testing

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