Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
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. |
Ce |
RCV003222226 | SCV003917204 | uncertain significance | not provided | 2023-01-01 | criteria provided, single submitter | clinical testing | LRRK2: PM2:Supporting, BP4 |