Decoding of novel missense TSC2 gene variants using in-silico methods

Area of Science:

• Genetics
• Molecular Biology
• Bioinformatics

Background:

• Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in TSC1 or TSC2 genes.
• TSC is characterized by hamartoma formation in multiple organs.
• TSC1 and TSC2 gene products form a heterodimer controlling mTORC1 signaling.

Purpose of the Study:

• To identify and characterize novel variants in TSC1 and TSC2 genes in TSC patients.
• To assess the pathogenicity of identified variants using bioinformatics and protein modeling.
• To understand the impact of novel missense variants on TSC protein function and interactions.

Main Methods:

• Genetic analysis of TSC1 and TSC2 genes in 98 TSC patients.
• Identification of 14 novel missense variations.
• Bioinformatics tools and computer-aided protein modeling for pathogenicity assessment.
• Structure prediction using homology modeling and fold recognition (Phyre2).

Main Results:

• 14 novel missense variations were identified in TSC1 and TSC2 genes.
• Protein modeling was successfully performed for ten variants within functional protein regions.
• Specific template structures were identified for modeling key protein domains.

Conclusions:

• The study assessed the impact of novel missense variants on TSC1-TSC2 hydrophobic interactions.
• The findings provide insights into the effect of these variants on protein function.
• This research contributes to understanding the molecular basis of tuberous sclerosis complex.