Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002330455 | SCV002633697 | uncertain significance | Inborn genetic diseases | 2022-01-21 | criteria provided, single submitter | clinical testing | The p.K1551E variant (also known as c.4651A>G), located in coding exon 32 of the LRRK2 gene, results from an A to G substitution at nucleotide position 4651. The lysine at codon 1551 is replaced by glutamic acid, an amino acid with similar 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. |
| Labcorp Genetics |
RCV005096619 | SCV005816014 | uncertain significance | Autosomal dominant Parkinson disease 8 | 2024-08-15 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 1551 of the LRRK2 protein (p.Lys1551Glu). This variant is not present in population databases (gnomAD no frequency). 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: 1742185). 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. |