Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_000548.5(TSC2):āc.1036A>Gā(p.Ile346Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
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]
Computational evidence support a benign effect (MetaRNN=0.16404328).
BP6
Variant 16-2060730-A-G is Benign according to our data. Variant chr16-2060730-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 406037.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.
Review Status: criteria provided, single submitter
Collection Method: clinical testing
The p.I346V variant (also known as c.1036A>G), located in coding exon 10 of the TSC2 gene, results from an A to G substitution at nucleotide position 1036. The isoleucine at codon 346 is replaced by valine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. -
Tuberous sclerosis 2 Benign:1
Jan 15, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Gain of methylation at K347 (P = 0.0849);Gain of methylation at K347 (P = 0.0849);Gain of methylation at K347 (P = 0.0849);.;Gain of methylation at K347 (P = 0.0849);Gain of methylation at K347 (P = 0.0849);Gain of methylation at K347 (P = 0.0849);Gain of methylation at K347 (P = 0.0849);.;Gain of methylation at K347 (P = 0.0849);Gain of methylation at K347 (P = 0.0849);Gain of methylation at K347 (P = 0.0849);Gain of methylation at K347 (P = 0.0849);Gain of methylation at K347 (P = 0.0849);.;