ClinVar Miner

Submissions for variant NM_198578.4(LRRK2):c.4165G>A (p.Val1389Ile)

gnomAD frequency: 0.00011  dbSNP: rs140743795
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001110111 SCV001267505 uncertain significance Autosomal dominant Parkinson disease 8 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae RCV001110111 SCV002119447 uncertain significance Autosomal dominant Parkinson disease 8 2021-09-08 criteria provided, single submitter clinical testing 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 881230). This variant has been observed in individual(s) with Parkinson disease (PMID: 27094865). This variant is present in population databases (rs140743795, ExAC 0.03%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This sequence change replaces valine with isoleucine at codon 1389 of the LRRK2 protein (p.Val1389Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine.
CeGaT Center for Human Genetics Tuebingen RCV003222226 SCV003917204 uncertain significance not provided 2023-01-01 criteria provided, single submitter clinical testing LRRK2: PM2:Supporting, BP4

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.