Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001968207 | SCV002238098 | uncertain significance | Autosomal dominant Parkinson disease 8 | 2020-12-03 | 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. 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"). This variant has not been reported in the literature in individuals with LRRK2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with cysteine at codon 596 of the LRRK2 protein (p.Tyr596Cys). The tyrosine residue is weakly conserved and there is a large physicochemical difference between tyrosine and cysteine. |
| Ambry Genetics | RCV003303507 | SCV004001661 | uncertain significance | Inborn genetic diseases | 2023-06-05 | criteria provided, single submitter | clinical testing | The p.Y596C variant (also known as c.1787A>G), located in coding exon 15 of the LRRK2 gene, results from an A to G substitution at nucleotide position 1787. The tyrosine at codon 596 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |