Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000700407 | SCV000829161 | uncertain significance | Desmin-related myofibrillar myopathy | 2024-12-04 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 189 of the DES protein (p.Arg189Trp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DES-related conditions. ClinVar contains an entry for this variant (Variation ID: 577606). Invitae Evidence 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 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. |
| Ambry Genetics | RCV002343524 | SCV002653791 | uncertain significance | Cardiovascular phenotype | 2021-04-30 | criteria provided, single submitter | clinical testing | The p.R189W variant (also known as c.565C>T), located in coding exon 1 of the DES gene, results from a C to T substitution at nucleotide position 565. The arginine at codon 189 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Revvity Omics, |
RCV003144550 | SCV003829006 | uncertain significance | not provided | 2021-01-20 | criteria provided, single submitter | clinical testing | |
| Genomic Medicine Center of Excellence, |
RCV000700407 | SCV005374247 | uncertain significance | Desmin-related myofibrillar myopathy | 2024-09-22 | criteria provided, single submitter | clinical testing |