Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002023501 | SCV002304634 | uncertain significance | Autosomal dominant Parkinson disease 8 | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine with serine at codon 1148 of the LRRK2 protein (p.Phe1148Ser). The phenylalanine residue is weakly conserved and there is a large physicochemical difference between phenylalanine and serine. This variant is present in population databases (rs774993871, ExAC 0.001%). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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 | RCV002454304 | SCV002617021 | uncertain significance | Inborn genetic diseases | 2023-11-23 | criteria provided, single submitter | clinical testing | The p.F1148S variant (also known as c.3443T>C), located in coding exon 25 of the LRRK2 gene, results from a T to C substitution at nucleotide position 3443. The phenylalanine at codon 1148 is replaced by serine, an amino acid with highly dissimilar 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. |