Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000807045 | SCV000947073 | uncertain significance | Parkinson disease 17 | 2022-12-10 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs370401767, gnomAD 0.009%). This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 474 of the VPS35 protein (p.Gln474Glu). This variant has not been reported in the literature in individuals affected with VPS35-related conditions. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt VPS35 protein function. ClinVar contains an entry for this variant (Variation ID: 651640). |
| Illumina Laboratory Services, |
RCV000807045 | SCV001273913 | benign | Parkinson disease 17 | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. |