Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000479420 | SCV000574123 | uncertain significance | not provided | 2017-03-17 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the PRX gene. The R228C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R228C variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R228C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Invitae | RCV000688877 | SCV000816504 | uncertain significance | Charcot-Marie-Tooth disease type 4 | 2018-07-09 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 228 of the PRX protein (p.Arg228Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with PRX-related disease. ClinVar contains an entry for this variant (Variation ID: 424325). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). 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. |
| Molecular Genetics Laboratory, |
RCV001173058 | SCV001336133 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing |