Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Fulgent Genetics, |
RCV000032481 | SCV002776060 | uncertain significance | Autosomal dominant Parkinson disease 8 | 2022-03-14 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000032481 | SCV002960943 | uncertain significance | Autosomal dominant Parkinson disease 8 | 2025-01-08 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 1728 of the LRRK2 protein (p.Arg1728Leu). This variant is present in population databases (rs145364431, gnomAD 0.006%). This missense change has been observed in individual(s) with Parkinsons disease (PMID: 18213618). ClinVar contains an entry for this variant (Variation ID: 39207). 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) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on LRRK2 protein function. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on LRRK2 function (PMID: 19625296, 20642453, 35950872). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
| Gene |
RCV000032481 | SCV000056142 | not provided | Autosomal dominant Parkinson disease 8 | no assertion provided | literature only |