Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001381342 | SCV001579680 | pathogenic | Tuberous sclerosis 2 | 2016-04-07 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 4-11 of the TSC2 gene. This leads to an in-frame deletion, preserving the integrity of the reading frame. This gross deletion encompasses a portion of the coiled-coil domain in TSC2 (amino acids 346–371) that mediates the interaction with TSC1 (PMID: 11741833, 9580671). An in-frame deletion of a single amino acid (p.Ile365del) in this region disrupts TSC1 binding (PMID: 11741833) and has been reported in multiple TSC patients (PMID: 10205261, 11112665), further emphasizing the importance of this domain. Deletions of exons 4-11 of TSC2 have not been reported in the literature. For these reasons, this variant has been classified as Pathogenic. |