Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center of Genomic medicine, |
RCV000857243 | SCV000999830 | likely pathogenic | Peroxisome biogenesis disorder 1A (Zellweger) | 2019-03-05 | criteria provided, single submitter | clinical testing | This variant was identified in combination with a second variant in trans in the same gene (PEX6 - composite heterozygosity) in a newborn patient with Zellweger syndrome |
Invitae | RCV002538893 | SCV003454373 | uncertain significance | Peroxisome biogenesis disorder | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with serine at codon 749 of the PEX6 protein (p.Gly749Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected 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 disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |