Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001578132 | SCV001805668 | uncertain significance | not provided | 2020-01-23 | criteria provided, single submitter | clinical testing | Reported in association with Parkinson disease; however, additional clinical information and segregation information were not provided (Ghani et al., 2015; Latourelle et al., 2011); Published functional studies are inconclusive as to whether the variant alters protein function and structure (Nichols et al., 2010; Doggett et al., 2012); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 21661047, 30049590, 24488318, 21885347, 19472409, 17804834, 22004453, 20642453, 25174650) |
Invitae | RCV000032482 | SCV002177329 | uncertain significance | Autosomal dominant Parkinson disease 8 | 2022-01-01 | 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. Experimental studies have shown that this missense change affects LRRK2 function (PMID: 20642453, 22004453). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 39208). This missense change has been observed in individual(s) with Parkinson disease (PMID: 17804834, 25174650, 27094865). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1795 of the LRRK2 protein (p.Leu1795Phe). |
Gene |
RCV000032482 | SCV000056143 | not provided | Autosomal dominant Parkinson disease 8 | no assertion provided | literature only |