ClinVar Miner

Submissions for variant NM_000466.3(PEX1):c.1991T>C (p.Leu664Pro)

gnomAD frequency: 0.00001  dbSNP: rs121434455
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000007949 SCV000220370 likely pathogenic Peroxisome biogenesis disorder 1A (Zellweger) 2014-06-05 criteria provided, single submitter literature only
Fulgent Genetics, Fulgent Genetics RCV000763597 SCV000894442 likely pathogenic Peroxisome biogenesis disorder 1A (Zellweger); Heimler syndrome 1; Peroxisome biogenesis disorder 1B 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV001248383 SCV001421866 likely pathogenic Zellweger spectrum disorders 2023-07-24 criteria provided, single submitter clinical testing 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. Experimental studies have shown that this missense change affects PEX1 function (PMID: 9539740, 11439091). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PEX1 protein function. ClinVar contains an entry for this variant (Variation ID: 7517). This missense change has been observed in individual(s) with Zellweger syndrome (PMID: 9539740). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 664 of the PEX1 protein (p.Leu664Pro).
Baylor Genetics RCV003473054 SCV004203304 likely pathogenic Heimler syndrome 1 2023-08-10 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV003480024 SCV004227040 likely pathogenic not provided 2023-04-12 criteria provided, single submitter clinical testing PP3, PM2, PS3
OMIM RCV000007949 SCV000028154 pathogenic Peroxisome biogenesis disorder 1A (Zellweger) 1998-04-14 no assertion criteria provided literature only
Natera, Inc. RCV001248383 SCV002076881 uncertain significance Zellweger spectrum disorders 2020-08-12 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.