Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000703546 | SCV000832449 | uncertain significance | Autosomal dominant Parkinson disease 8 | 2018-06-20 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with asparagine at codon 365 of the LRRK2 protein (p.His365Asn). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and asparagine. This variant is present in population databases (rs765509204, ExAC 0.002%). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with LRRK2-related disease. |
| Ambry Genetics | RCV002442521 | SCV002734313 | uncertain significance | Inborn genetic diseases | 2022-10-28 | criteria provided, single submitter | clinical testing | The p.H365N variant (also known as c.1093C>A), located in coding exon 9 of the LRRK2 gene, results from a C to A substitution at nucleotide position 1093. The histidine at codon 365 is replaced by asparagine, an amino acid with 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. |