Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
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, |
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, |
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. |