Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000590176 | SCV000697878 | uncertain significance | not provided | 2016-01-13 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000706363 | SCV000835407 | uncertain significance | Desmin-related myofibrillar myopathy | 2023-10-13 | 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 369 of the DES protein (p.Arg369Cys). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 496146). 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. |
| Ambry Genetics | RCV002438526 | SCV002745432 | uncertain significance | Cardiovascular phenotype | 2022-03-24 | criteria provided, single submitter | clinical testing | The p.R369C variant (also known as c.1105C>T), located in coding exon 6 of the DES gene, results from a C to T substitution at nucleotide position 1105. The arginine at codon 369 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly 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. |
| Fulgent Genetics, |
RCV002491167 | SCV002800173 | uncertain significance | Dilated cardiomyopathy 1I; Desmin-related myofibrillar myopathy; Neurogenic scapuloperoneal syndrome, Kaeser type | 2021-09-03 | criteria provided, single submitter | clinical testing |