Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000805282 | SCV000945233 | pathogenic | Duchenne muscular dystrophy | 2018-12-28 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 19-79 of the DMD gene. The 5' boundary is likely confined to intron 18. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation. This variant has not been reported in the literature in individuals with DMD-related conditions. Many smaller in-frame deletions in the deleted region have been determined to be pathogenic (PMID: 15723292, 26081009, 19937601, 20153965, 16834926). In addition, this variant disrupts the second actin-binding domain (ABD2) of the DMD protein, which is critical for DMD function (PMID: 26140716, 26676145). While functional studies have not been performed to directly test the effect of this variant on DMD protein function, this suggests that disruption of this region of the protein is causative of disease. For these reasons, this variant has been classified as Pathogenic. |