Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000807936 | SCV000948016 | uncertain significance | Autosomal dominant Parkinson disease 8 | 2020-01-11 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with LRRK2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with glutamine at codon 1632 of the LRRK2 protein (p.Glu1632Gln). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and glutamine. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003396412 | SCV004122230 | uncertain significance | not specified | 2023-10-26 | criteria provided, single submitter | clinical testing | Variant summary: LRRK2 c.4894G>C (p.Glu1632Gln) results in a conservative amino acid change located in the C-terminal of Roc (COR) domain (IPR032171) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 249712 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4894G>C has been reported in the literature in individuals affected with dementia with Lewy bodies or chronic obstructive pulmonary disease (Rubio_2012, Keogh_2018). These reports do not provide unequivocal conclusions about association of the variant with Parkinson Disease 8, Autosomal Dominant. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 22415848, 30363439, 29332010). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |