Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001299265 | SCV001488349 | uncertain significance | Desmin-related myofibrillar myopathy | 2023-08-25 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 13 of the DES protein (p.Ser13Pro). 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. This variant disrupts the p.Ser13 amino acid residue in DES. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17720647, 18061454, 19879535, 23349452, 26097489). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: 1002791). This variant has not been reported in the literature in individuals affected with DES-related conditions. This variant is not present in population databases (gnomAD no frequency). |
| Ambry Genetics | RCV003166680 | SCV003878366 | uncertain significance | Cardiovascular phenotype | 2023-02-24 | criteria provided, single submitter | clinical testing | The p.S13P variant (also known as c.37T>C), located in coding exon 1 of the DES gene, results from a T to C substitution at nucleotide position 37. The serine at codon 13 is replaced by proline, 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. |