Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV003205890 | SCV003908170 | uncertain significance | Inborn genetic diseases | 2023-08-14 | criteria provided, single submitter | clinical testing | The c.724C>T (p.L242F) alteration is located in exon 7 (coding exon 7) of the LRRK2 gene. This alteration results from a C to T substitution at nucleotide position 724, causing the leucine (L) at amino acid position 242 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003638922 | SCV004511917 | uncertain significance | Autosomal dominant Parkinson disease 8 | 2024-12-10 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 242 of the LRRK2 protein (p.Leu242Phe). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with LRRK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2489685). Invitae Evidence 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 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. 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. |