ClinVar Miner

Submissions for variant NM_000287.4(PEX6):c.1992G>C (p.Glu664Asp)

gnomAD frequency: 0.00002  dbSNP: rs267608230
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001248070 SCV001421535 uncertain significance Peroxisome biogenesis disorder 2022-01-17 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 664 of the PEX6 protein (p.Glu664Asp). This variant is present in population databases (rs267608230, gnomAD 0.02%). This missense change has been observed in individual(s) with Zellweger Syndrome Spectrum (PMID: 19877282, 26287655). ClinVar contains an entry for this variant (Variation ID: 972112). 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: "Benign"; 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.
Fulgent Genetics, Fulgent Genetics RCV002480855 SCV002782887 uncertain significance Peroxisome biogenesis disorder 4A (Zellweger); Peroxisome biogenesis disorder 4B; Heimler syndrome 2 2021-10-13 criteria provided, single submitter clinical testing
Baylor Genetics RCV003473835 SCV004201540 likely pathogenic Heimler syndrome 2 2024-02-26 criteria provided, single submitter clinical testing
Natera, Inc. RCV001836248 SCV002077289 uncertain significance Zellweger spectrum disorders 2020-03-06 no assertion criteria provided clinical testing
Next Generation Genetic Polyclinic RCV004697090 SCV005184165 likely pathogenic Peroxisome biogenesis disorder 4A (Zellweger) 2024-08-07 no assertion criteria provided clinical testing The NM_000287.4 c.1992G>C variant in the PEX6 gene is a missense mutation that results in the substitution of glycine with arginine at codon 664 (p.Gly664Arg). This variant has been identified as mutated homozygous in the proband and heterozygous in her parent using Sanger sequencing method. This variant has been reported in individuals with peroxisomal biogenesis disorders, suggesting a potential pathogenic role. Using predictive tools such as SIFT and PolyPhen, this variant is assessed as likely deleterious. SIFT suggests that it may disrupt protein function, while PolyPhen indicates that it could be damaging to the protein's structure. In summary, this variant aligns with criteria set forth by the ClinGen PEX6 VCEP, indicating it may contribute to the patient's clinical presentation and warrant further investigation for potential implications in diagnosis and management. Functional studies are needed to elucidate the impact of this variant on protein function. Further evidence, including co-segregation analysis and population frequency data, should be considered to assess its clinical significance.

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.