ClinVar Miner

Submissions for variant NM_000466.3(PEX1):c.3077T>C (p.Leu1026Pro)

dbSNP: rs954814470
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000669293 SCV000794033 uncertain significance Peroxisome biogenesis disorder 1A (Zellweger) 2017-11-14 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000729582 SCV000857255 uncertain significance not provided 2017-10-10 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002531221 SCV001204911 likely pathogenic Zellweger spectrum disorders 2024-03-18 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 1026 of the PEX1 protein (p.Leu1026Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Zellweger spectrum disorders (PMID: 28446956, 32483926, 33955814, 35322241). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 553776). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PEX1 protein function with a positive predictive value of 80%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Baylor Genetics RCV001332474 SCV001524808 uncertain significance Peroxisome biogenesis disorder 1B 2019-12-04 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Baylor Genetics RCV003472113 SCV004203315 pathogenic Heimler syndrome 1 2024-03-14 criteria provided, single submitter clinical testing
GeneDx RCV000729582 SCV005327860 likely pathogenic not provided 2023-08-18 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: 32483926, 35322241, 33708531, 31374812, 36511274, Parsamanesh2021[Case Report], 28446956, 33955814)

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