ClinVar Miner

Submissions for variant NM_000466.3(PEX1):c.2021C>T (p.Pro674Leu)

gnomAD frequency: 0.00006  dbSNP: rs141509344
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000395782 SCV000345640 uncertain significance not provided 2018-02-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002519349 SCV003268661 uncertain significance Zellweger spectrum disorders 2022-09-15 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 674 of the PEX1 protein (p.Pro674Leu). This variant is present in population databases (rs141509344, gnomAD 0.01%). This missense change has been observed in individual(s) with PEX1-related conditions (PMID: 32203225). ClinVar contains an entry for this variant (Variation ID: 290970). 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 not expected to disrupt PEX1 protein function. 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.
Ambry Genetics RCV002519350 SCV003706190 uncertain significance Inborn genetic diseases 2021-09-15 criteria provided, single submitter clinical testing (Thomas, 2020) Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV005396905 SCV006058054 uncertain significance Peroxisome biogenesis disorder 1A (Zellweger); Heimler syndrome 1; Peroxisome biogenesis disorder 1B 2023-09-21 criteria provided, single submitter research
PreventionGenetics, part of Exact Sciences RCV004752836 SCV005353336 uncertain significance PEX1-related disorder 2024-09-04 no assertion criteria provided clinical testing The PEX1 c.2021C>T variant is predicted to result in the amino acid substitution p.Pro674Leu. This variant was reported in an individual with Zellweger syndrome, who also had two pathogenic variants in PEX1 (Thomas et al. 2020. PubMed ID: 32203225). This variant is reported in 0.0099% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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