Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002045244 | SCV002295992 | uncertain significance | Autosomal dominant Parkinson disease 8 | 2021-10-14 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with LRRK2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a 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. This sequence change replaces methionine with isoleucine at codon 1607 of the LRRK2 protein (p.Met1607Ile). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is not present in population databases (ExAC no frequency). |
| Ambry Genetics | RCV002337127 | SCV002635052 | uncertain significance | Inborn genetic diseases | 2024-04-13 | criteria provided, single submitter | clinical testing | The p.M1607I variant (also known as c.4821G>A), located in coding exon 33 of the LRRK2 gene, results from a G to A substitution at nucleotide position 4821. The methionine at codon 1607 is replaced by isoleucine, an amino acid with highly 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. |