Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003779826 | SCV004570476 | uncertain significance | Desmin-related myofibrillar myopathy | 2023-06-16 | 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. 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: 2502282). This variant has not been reported in the literature in individuals affected with DES-related conditions. This variant is present in population databases (rs753305257, gnomAD 0.0009%). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 425 of the DES protein (p.Ala425Pro). |
| Ambry Genetics | RCV004285627 | SCV005018049 | uncertain significance | Cardiovascular phenotype | 2023-11-04 | criteria provided, single submitter | clinical testing | The p.A425P variant (also known as c.1273G>C), located in coding exon 7 of the DES gene, results from a G to C substitution at nucleotide position 1273. The alanine at codon 425 is replaced by proline, an amino acid with highly similar properties. This amino acid position is conserved. 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. |
| Genome |
RCV003228700 | SCV003925460 | not provided | Dilated cardiomyopathy 1I; Desmin-related myofibrillar myopathy | no assertion provided | phenotyping only | Variant interpreted as Uncertain significance and reported on 02-13-2023 by Invitae. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. |