ClinVar Miner

Submissions for variant NM_181882.2(PRX):c.2449C>T (p.Arg817Cys) (rs147441856)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235654 SCV000292809 uncertain significance not specified 2015-04-23 criteria provided, single submitter clinical testing The R817C has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. It was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The R817C 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 across species. Additionally, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with PRX-related disorders (Stenson et al., 2014). 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 or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina RCV000654055 SCV000413224 uncertain significance Charcot-Marie-Tooth disease type 4 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000654055 SCV000775945 uncertain significance Charcot-Marie-Tooth disease type 4 2018-12-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 817 of the PRX protein (p.Arg817Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs147441856, ExAC 0.03%). This variant has not been reported in the literature in individuals with PRX-related disease. ClinVar contains an entry for this variant (Variation ID: 245733). 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; 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.

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