Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000400697 | SCV000378622 | likely benign | Autosomal dominant Parkinson disease 8 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
Invitae | RCV000400697 | SCV000947858 | uncertain significance | Autosomal dominant Parkinson disease 8 | 2018-11-12 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with LRRK2-related disease. ClinVar contains an entry for this variant (Variation ID: 308640). This variant is present in population databases (rs754436306, ExAC 0.07%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This sequence change replaces valine with leucine at codon 1905 of the LRRK2 protein (p.Val1905Leu). The valine residue is highly conserved and there is a small physicochemical difference between valine and leucine. |