ClinVar Miner

Submissions for variant NM_000287.4(PEX6):c.224T>C (p.Leu75Pro)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003027061 SCV003326080 uncertain significance Peroxisome biogenesis disorder 2022-03-16 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 75 of the PEX6 protein (p.Leu75Pro). 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. 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"). This variant has not been reported in the literature in individuals affected with PEX6-related conditions. This variant is not present in population databases (gnomAD no frequency).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003994483 SCV004813546 uncertain significance not specified 2024-02-20 criteria provided, single submitter clinical testing Variant summary: PEX6 c.224T>C (p.Leu75Pro) results in a non-conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 88790 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.224T>C in individuals affected with Peroxisome Biogenesis Disorder and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2112925). Based on the evidence outlined above, the variant was classified as uncertain significance.

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