Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001916110 | SCV002178156 | uncertain significance | Huntington disease-like 1 | 2024-10-22 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 208 of the PRNP protein (p.Arg208Cys). This variant is present in population databases (rs55826236, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with PRNP-related conditions. ClinVar contains an entry for this variant (Variation ID: 1409869). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt PRNP protein function with a negative predictive value of 80%. This variant disrupts the p.Arg208 amino acid residue in PRNP. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 2458274, 8909447, 15739100, 15753435, 16533975). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |