Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000463416 | SCV000548835 | uncertain significance | Charcot-Marie-Tooth disease, axonal, type 2O | 2019-11-08 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 1771 of the DYNC1H1 protein (p.Gly1771Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs139842853, ExAC 0.02%) but has not been reported in the literature in individuals with a DYNC1H1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Genetic Services Laboratory, |
RCV000502250 | SCV000594441 | likely benign | not specified | 2016-10-05 | criteria provided, single submitter | clinical testing | |
| Illumina Clinical Services Laboratory, |
RCV000463416 | SCV001272439 | likely benign | Charcot-Marie-Tooth disease, axonal, type 2O | 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. |
| Illumina Clinical Services Laboratory, |
RCV001114542 | SCV001272440 | likely benign | Autosomal dominant cerebellar ataxia | 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. |
| Centre for Mendelian Genomics, |
RCV000414779 | SCV000492652 | uncertain significance | Myopathy; Muscle weakness | 2016-02-17 | no assertion criteria provided | clinical testing |