Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000697494 | SCV000826108 | pathogenic | Tuberous sclerosis 2 | 2018-03-15 | criteria provided, single submitter | clinical testing | This sequence change deletes the last 29 nucleotides of the coding sequence of TSC2 as well as part of the 3'UTR (c.5393_*57del), causing a frameshift at codon 1798. This creates a frameshift in the last exon of the TSC2 mRNA (p.Ser1798Tyrfs*?). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 11 amino acids of the TSC2 protein, including the termination codon, and extends the reading frame to a new termination codon outside of the TSC2 3'UTR. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TSC2-related disease. A different variant (c.5405_5408dupACTT), that also disrupts the TSC2 termination codon and extends the reading frame past the TSC2 3'UTR (p.Pro1803Leufs*?), lies downstream of this variant and has been determined to be pathogenic (PMID: 24789117). This suggests that disruption of this region of the TSC2 protein is causative of disease. For these reasons, this variant has been classified as Pathogenic. |