Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003873881 | SCV004680154 | uncertain significance | Autosomal dominant Parkinson disease 8 | 2023-11-22 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 948 of the LRRK2 protein (p.Arg948Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LRRK2-related conditions. 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 LRRK2 protein function with a negative predictive value of 80%. 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. |
| Ambry Genetics | RCV004636874 | SCV005135791 | uncertain significance | Inborn genetic diseases | 2024-04-09 | criteria provided, single submitter | clinical testing | The p.R948G variant (also known as c.2842C>G), located in coding exon 22 of the LRRK2 gene, results from a C to G substitution at nucleotide position 2842. The arginine at codon 948 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |