Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Fulgent Genetics, |
RCV000023115 | SCV002800210 | pathogenic | Parkinson disease 17 | 2021-07-03 | criteria provided, single submitter | clinical testing | |
3billion | RCV000023115 | SCV004013790 | pathogenic | Parkinson disease 17 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (3Cnet: 0.60). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000030196 / PMID: 21763482). The variant has been observed in multiple (>3) similarly affected unrelated individuals (PMID: 21763482, 21763483, 22801713, 22991136). The variant has been reported to co-segregate with the disease in at least 7 similarly affected relatives/individuals in at least two unrelated families (PMID: 21763482, 21763483, 22801713, 22991136). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. | |
Invitae | RCV000023115 | SCV004297720 | pathogenic | Parkinson disease 17 | 2023-03-08 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 620 of the VPS35 protein (p.Asp620Asn). Experimental studies have shown that this missense change affects VPS35 function (PMID: 23411763, 24740878). For these reasons, this variant has been classified as Pathogenic. 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 expected to disrupt VPS35 protein function. ClinVar contains an entry for this variant (Variation ID: 30196). This missense change has been observed in individual(s) with Parkinson disease (PMID: 21763482, 22154191, 22801713). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). |
OMIM | RCV000023115 | SCV000044406 | pathogenic | Parkinson disease 17 | 2012-10-01 | no assertion criteria provided | literature only | |
Gene |
RCV000023115 | SCV000679666 | not provided | Parkinson disease 17 | no assertion provided | literature only |