Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000214253 | SCV000271621 | uncertain significance | not specified | 2015-10-22 | criteria provided, single submitter | clinical testing | The p.Val126Leu variant in DES has not been previously reported in individuals w ith cardiomyopathy. Data from large population studies is insufficient to assess the frequency of this variant. Computational prediction tools and conservation analysis suggest that the p.Val126Leu variant may impact the protein, though thi s information is not predictive enough to determine pathogenicity. In summary, t he clinical significance of the p.Val126Leu variant is uncertain. |
Invitae | RCV000820863 | SCV000961596 | uncertain significance | Desmin-related myofibrillar myopathy | 2023-07-07 | 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 sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 126 of the DES protein (p.Val126Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with dilated cardiomyopathy or left ventricular noncompaction (PMID: 25163546, 32746448, 33500567). ClinVar contains an entry for this variant (Variation ID: 228549). 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) performed at Invitae indicates that this missense variant is expected to disrupt DES protein function. |