Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002640053 | SCV002982633 | uncertain significance | Peroxisome biogenesis disorder | 2021-09-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with leucine at codon 175 of the PEX6 protein (p.Arg175Leu). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PEX6-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
Prevention |
RCV004548350 | SCV004114205 | uncertain significance | PEX6-related disorder | 2022-10-06 | criteria provided, single submitter | clinical testing | The PEX6 c.524G>T variant is predicted to result in the amino acid substitution p.Arg175Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0088% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-42946365-C-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |