Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000824328 | SCV000965222 | uncertain significance | Desmin-related myofibrillar myopathy | 2022-09-20 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 78 of the DES protein (p.Arg78Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 201717). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
| Fulgent Genetics, |
RCV002478625 | SCV002791538 | uncertain significance | Dilated cardiomyopathy 1I; Desmin-related myofibrillar myopathy; Neurogenic scapuloperoneal syndrome, Kaeser type | 2021-11-23 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004020210 | SCV005018343 | uncertain significance | Cardiovascular phenotype | 2023-12-18 | criteria provided, single submitter | clinical testing | The p.R78L variant (also known as c.233G>T), located in coding exon 1 of the DES gene, results from a G to T substitution at nucleotide position 233. The arginine at codon 78 is replaced by leucine, an amino acid with dissimilar properties. This variant has been detected in individuals from dilated cardiomyopathy cohorts; however, details were limited (Mazzarotto F et al. Circulation, 2020 Feb;141:387-398; Shen C et al. Ann Transl Med, 2022 Feb;10:129). This amino acid position is 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. |