Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000559463 | SCV000654171 | uncertain significance | Desmin-related myofibrillar myopathy | 2023-08-25 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 90 of the DES protein (p.Asp90His). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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. 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. ClinVar contains an entry for this variant (Variation ID: 474287). This variant has not been reported in the literature in individuals affected with DES-related conditions. |
Ambry Genetics | RCV002431698 | SCV002742294 | uncertain significance | Cardiovascular phenotype | 2022-03-24 | criteria provided, single submitter | clinical testing | The p.D90H variant (also known as c.268G>C), located in coding exon 1 of the DES gene, results from a G to C substitution at nucleotide position 268. The aspartic acid at codon 90 is replaced by histidine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |