Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000227930 | SCV000287214 | likely pathogenic | Desmin-related myofibrillar myopathy | 2022-11-29 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 338 of the DES protein (p.Leu338Pro). This variant disrupts the p.Leu338 amino acid residue in DES. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16865695). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant is not present in population databases (gnomAD no frequency). 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. ClinVar contains an entry for this variant (Variation ID: 239071). This variant has not been reported in the literature in individuals affected with DES-related conditions. |