Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000548.5(TSC2):c.2986A>T(p.Thr996Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
TSC2 (HGNC:12363): (TSC complex subunit 2) This gene is a tumor suppressor gene that encodes the growth inhibitory protein tuberin. Tuberin interacts with hamartin to form the TSC protein complex which functions in the control of cell growth. This TSC protein complex negatively regulates mammalian target of rapamycin complex 1 (mTORC1) signaling which is a major regulator of anabolic cell growth. Mutations in this gene have been associated with tuberous sclerosis and lymphangioleiomyomatosis. [provided by RefSeq, May 2022]
Review Status: criteria provided, single submitter
Collection Method: clinical testing
The p.T996S variant (also known as c.2986A>T), located in coding exon 26 of the TSC2 gene, results from an A to T substitution at nucleotide position 2986. The threonine at codon 996 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. -
Gain of phosphorylation at T996 (P = 0.0401);.;Gain of phosphorylation at T996 (P = 0.0401);.;.;.;.;Gain of phosphorylation at T996 (P = 0.0401);.;Gain of phosphorylation at T996 (P = 0.0401);.;.;.;.;.;