Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000056782 | SCV000235791 | pathogenic | not provided | 2019-09-19 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate that E413K caused defects in filament formation and indicated that the cellular filamentous networking properties were impaired, and showed that dot-like aggregates were accumulated throughout the cytoplasm of muscle fibers (Pruszczyk et al., 2007; Bar et al., 2007; Levin et al., 2010; Chourbagi et al., 2011); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Reported in ClinVar as likely pathogenic (ClinVar Variant ID# 66398; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 28269794, 19587455, 21262226, 20448486, 16890305, 17221859, 23425003, 26789769) |
| Invitae | RCV000685786 | SCV000813283 | likely pathogenic | Desmin-related myofibrillar myopathy | 2021-12-17 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects DES function (PMID: 16890305, 17221859, 20448486, 21262226, 23425003, 26789769). 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: "Probably Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 66398). This missense change has been observed in individuals with clinical features of autosomal dominant DES-related conditions (PMID: 16890305; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 413 of the DES protein (p.Glu413Lys). |
| Epithelial Biology; Institute of Medical Biology, |
RCV000056782 | SCV000087895 | not provided | not provided | no assertion provided | not provided |