Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000471643 | SCV000552173 | uncertain significance | Desmin-related myofibrillar myopathy | 2016-11-02 | criteria provided, single submitter | clinical testing | In summary, this variant is a novel missense change with uncertain impact on protein function. 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class 0"). This variant is present in population databases (rs1135931, ExAC <0.01%) but has not been reported in the literature in individuals with a DES-related disease. This sequence change replaces alanine with glutamine at codon 462 of the DES protein (p.Ala462Glu). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and glutamine. |
| Gene |
RCV001770353 | SCV001992677 | uncertain significance | not provided | 2019-06-11 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Reported as a variant of uncertain significance in ClinVar but additional evidence is not available (ClinVar Variant ID#411144; Landrum et al., 2016); Deletion of two nucleotides and insertion of two nucleotides that results in the in frame substitution of one amino acid residue; in silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function |