Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV004582703 | SCV005062293 | pathogenic | Tuberous sclerosis 2 | 2016-03-07 | criteria provided, single submitter | clinical testing | This sequence change is a complex rearrangement involving the final exon of the TSC2 gene. 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. This sequence change results in a frameshift at codon 1791 in exon 42 of the TSC2 mRNA. This is predicted to create a premature translational stop signal (p.Gly1791Valfs*14). While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TSC2 protein by replacing the last 17 amino acids with 14 random amino acids. For these reasons, this variant has been classified as Pathogenic. While this particular variant has not been reported in the literature, a frameshift variant, c.5405_5408dup (p.Phe1803Leufs*42), located downstream of the 5' end of this event has been reported as a disease-causing de novo variant in an individual affected with tuberous sclerosis complex (TSC) (PMID: 24789117), suggesting that frameshift variants affecting the very C-terminal of TSC2 impact protein function and cause disease. |