Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000037231 | SCV000060888 | uncertain significance | not specified | 2012-08-27 | criteria provided, single submitter | clinical testing | The Gly456Arg variant in DES has not been reported in the literature nor previou sly identified by our laboratory. Computational analyses (biochemical amino acid properties, conservation, PolyPhen2, and SIFT) suggest that this variant may im pact the protein, though this information is not predictive enough to determine pathogenicity. Additional information is needed to fully assess the clinical sig nificance of this variant. |
| Labcorp Genetics |
RCV001852772 | SCV002196116 | uncertain significance | Desmin-related myofibrillar myopathy | 2024-06-03 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 456 of the DES protein (p.Gly456Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 32150461). ClinVar contains an entry for this variant (Variation ID: 44251). 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. |
| Neurogenomics Lab, |
RCV001852772 | SCV004708214 | likely pathogenic | Desmin-related myofibrillar myopathy | 2024-05-22 | criteria provided, single submitter | research | PM2_Supporting: This variant is absent from gnomAD v4.0 (adequate coverage >20x confirmed). PM1 not met: pathogenic DES variants are distributed throughout the protein. PP3_Moderate: REVEL score is 0.884. PM3 Met: max 1 point awarded for 2 homozygous observations of variant in probands with consistent phenotype for disorder. PS4_Supporting: Variant found in 1 proband (homozygous) with consistent phenotype for disorder. This proband counted under PS4 as max points reached for homozygous observations counted under PM3. Sequencing funded by the International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD): https://www.ucl.ac.uk/genomic-medicine-neuromuscular-diseases |