Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003513658 | SCV004298901 | likely pathogenic | Duchenne muscular dystrophy | 2023-10-23 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1815 of the DMD protein (p.Asp1815Gly). RNA analysis indicates that this missense change induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of Duchenne muscular dystrophy (PMID: 23536893; Invitae). 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 not expected to disrupt DMD protein function with a negative predictive value of 95%. Studies have shown that this missense change results in activation of cryptic splice site and introduces a premature termination codon (PMID: 23536893). The resulting mRNA is expected to undergo nonsense-mediated decay. 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. |