ClinVar Miner

Submissions for variant NM_001351132.2(PEX5):c.1799C>T (p.Ser600Leu)

gnomAD frequency: 0.00001  dbSNP: rs748956654
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480471 SCV000569744 likely pathogenic not provided 2023-02-27 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34534157, 27290639, 31597922)
Labcorp Genetics (formerly Invitae), Labcorp RCV001856846 SCV002155523 uncertain significance Peroxisome biogenesis disorder 2B 2022-07-05 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 600 of the PEX5 protein (p.Ser600Leu). This variant is present in population databases (rs748956654, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of PEX5-related conditions (PMID: 27290639). ClinVar contains an entry for this variant (Variation ID: 420777). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV005407140 SCV006072261 uncertain significance not specified 2025-03-31 criteria provided, single submitter clinical testing Variant summary: PEX5 c.1799C>T (p.Ser600Leu) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251350 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1799C>T has been reported in the literature in individuals affected with Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum (Pronicka_2016). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 27290639). ClinVar contains an entry for this variant (Variation ID: 420777). Based on the evidence outlined above, the variant was classified as uncertain significance.

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