Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001854271 | SCV002172212 | uncertain significance | Huntington disease-like 1 | 2021-10-05 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Glu211 amino acid residue in PRNP. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10790216, 11568919, 12590162, 22965875). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 88922). This variant is also known as c.633C>G. This missense change has been observed in individuals with clinical features of PRNP-related conditions (PMID: 22965875; Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with aspartic acid at codon 211 of the PRNP protein (p.Glu211Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. |
| OMIM | RCV000074467 | SCV000108506 | pathogenic | Gerstmann-Straussler-Scheinker syndrome | 2012-12-15 | no assertion criteria provided | literature only |