Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000795247 | SCV000934696 | uncertain significance | Tuberous sclerosis 2 | 2018-08-15 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with TSC2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the TSC2 gene (p.Tyr1788*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 20 amino acids of the TSC2 protein. Frameshift variants that extend the reading frame of the C-terminal end of the TSC2 protein have been observed in individuals affected with tuberous sclerosis complex (TSC) (PMID: 21520333, 24789117, 21520333, Invitae). However, while nonsense variants that remove this very C-terminal end of the TSC2 protein have been observed in several instances, the individuals do not have clinical features consistent with TSC (Invitae). 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. This variant is not expected to affect the Rap-GAP domain, which is required for tumor suppression function (PMID: 8799170, 18466115). Experimental studies are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. |