Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000522498 | SCV000620231 | uncertain significance | not provided | 2017-08-28 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the DES gene. The A213T variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is also not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A213T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Furthermore, this substitution occurs at a position that is conserved in mammals. Nevertheless, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Additionally, this variant has not been observed in a significant number of affected individuals, and it lacks both segregation and functional studies which would further clarify its pathogenicity. |
| Invitae | RCV000702212 | SCV000831056 | uncertain significance | Desmin-related myofibrillar myopathy | 2022-11-08 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 451514). This variant has not been reported in the literature in individuals affected with DES-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.004%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 213 of the DES protein (p.Ala213Thr). |
| Ambry Genetics | RCV003338638 | SCV004058501 | uncertain significance | Cardiovascular phenotype | 2023-09-20 | criteria provided, single submitter | clinical testing | The p.A213T variant (also known as c.637G>A), located in coding exon 2 of the DES gene, results from a G to A substitution at nucleotide position 637. The alanine at codon 213 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |