Computational Modelling of Human Sarcomeric Telethonin Protein and Predicting the Functional effect of Missense Single Nucleotide Polymorphsim

Telethonin (T-cap) is a 19 kDa protein and in humans it is encoded by the TCAP gene chr17q12. Telethonin is expressed in cardiac and skeletal muscle at Z-discs. Telethonin binds to the titin Z1–Z2 domains and is a substrate of titin kinase, interactions thought to be critical to sarcomere assembly. Variation in Telethonin implicates several diseases, including limb-girdle muscular dystrophy, cardiomyopathy, dilated and idiopathic cardiomyopathy. This protein variation study helps us understand the several cardiac and muscular disorders related to missense single nucleotide polymorphisms (SNPs) mutation and specified drug designing. Here we evaluate computational analysis of missense SNPs present in the TCAP gene. It was performed by considering 13 prediction tools in order to select the deleterious variations and followed by molecular modelling, evolutionary conservation analysis, signal peptide prediction and model validation. It has been found that eight deleterious variants, out of which three (Arg70Trp, Pro90Leu and Arg106Cys) are previously associated with human diseases.