Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000701695 | SCV000830507 | uncertain significance | Desmin-related myofibrillar myopathy | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 248 of the DES protein (p.Arg248Cys). This variant is present in population databases (rs772117708, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of DES-related conditions (PMID: 30975432). ClinVar contains an entry for this variant (Variation ID: 578625). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DES protein function. 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. |
| Gene |
RCV001797133 | SCV002039079 | uncertain significance | not provided | 2021-06-16 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 578625; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 27535533, 26582918) |