Submissions for variant NC_000016.9:g.(?_2133686)_(2138611_?)del

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001378863	SCV001576545	likely pathogenic	Tuberous sclerosis 2	2020-08-31	criteria provided, single submitter	clinical testing	This variant disrupts the p.Glu1552 amino acid residue in TSC2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11112665, 22903760, 23389244). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This variant has not been reported in the literature in individuals with TSC2-related conditions. This variant is a gross deletion of the genomic region encompassing exon(s) 33-42 of the TSC2 gene. The 5' boundary is likely confined to intron 32. 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. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.