Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000794180 | SCV000933571 | pathogenic | Desmin-related myofibrillar myopathy | 2023-02-08 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 66414). 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. Experimental studies have shown that this missense change affects DES function (PMID: 19763525). For these reasons, this variant has been classified as Pathogenic. This missense change has been observed in individuals with autosomal dominant myofibrillar myopathy (PMID: 14711882, 22153487, 25208129). This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 2 of the DES protein (p.Ser2Ile). This variant is not present in population databases (gnomAD no frequency). |
| Athena Diagnostics Inc | RCV000056804 | SCV004229575 | likely pathogenic | not provided | 2022-12-28 | criteria provided, single submitter | clinical testing | This variant has been identified in multiple unrelated individuals with clinical features of autosomal dominant myofibrillar myopathy. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Computational tools predict that this variant is damaging. |
| Epithelial Biology; Institute of Medical Biology, |
RCV000056804 | SCV000087917 | not provided | not provided | no assertion provided | not provided |