ClinVar Miner

Submissions for variant NM_000466.3(PEX1):c.1897C>T (p.Arg633Ter)

dbSNP: rs61750409
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665705 SCV000789869 likely pathogenic Peroxisome biogenesis disorder 1A (Zellweger) 2017-02-24 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193608 SCV001362556 pathogenic Peroxisome biogenesis disorder 2022-12-19 criteria provided, single submitter clinical testing Variant summary: PEX1 c.1897C>T (p.Arg633X) 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 4e-06 in 251234 control chromosomes. c.1897C>T has been reported in the literature in individuals affected with Peroxisome Biogenesis Disorder/Zellweger syndrome (example, Piscosquito_2016, Rosewich_2005, Tamura_2001, Alshenaifi_2019). These data indicate that the variant is likely to be associated with disease. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV001868206 SCV002143646 pathogenic Zellweger spectrum disorders 2022-11-24 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: 550841). This premature translational stop signal has been observed in individual(s) with PEX1-related conditions (PMID: 11439091). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Arg633*) 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).
Preventiongenetics, part of Exact Sciences RCV003420172 SCV004107951 pathogenic PEX1-related condition 2023-01-03 criteria provided, single submitter clinical testing The PEX1 c.1897C>T variant is predicted to result in premature protein termination (p.Arg633*). This variant has been reported in patients with PEX1-related disorders (Patient E-13 in Tamura et al. 2001. PubMed ID: 11439091; Abualsaud et al. 2020. PubMed ID: 32949114; Shamseldin et al. 2021. PubMed ID: 34645488; Rosewich et al. 2005. PubMed ID: 16141001). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/7-92135565-G-A). Nonsense variants in PEX1 are expected to be pathogenic. This variant is interpreted as pathogenic.
Baylor Genetics RCV003472072 SCV004203259 pathogenic Heimler syndrome 1 2023-10-29 criteria provided, single submitter clinical testing

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