Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002383552 | SCV002696040 | uncertain significance | Inborn genetic diseases | 2024-11-03 | criteria provided, single submitter | clinical testing | The p.S455P variant (also known as c.1363T>C), located in coding exon 12 of the LRRK2 gene, results from a T to C substitution at nucleotide position 1363. The serine at codon 455 is replaced by proline, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003095037 | SCV003481299 | uncertain significance | Autosomal dominant Parkinson disease 8 | 2022-10-05 | 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. 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) has been performed at Invitae 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. This variant has not been reported in the literature in individuals affected with LRRK2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 455 of the LRRK2 protein (p.Ser455Pro). |