TITINdb2 - Expanding Annotation and Structural Information for Protein Variants in the Giant Sarcomeric Protein Titin

Abstract

Structured AbstractO_ST_ABSSummaryC_ST_ABSWe present TITINdb2, an update to the TITINdb database previously constructed to facilitate the identification of pathogenic missense variants in the giant protein titin, which are associated with a variety of skeletal and cardiac myopathies. The database and web portal have been substantially revised and include the following new features: (i) an increase in computational annotation from 4 to 20 variant impact predictors, available through a new custom data table dialogue; (ii) thorough structural coverage of single domains with AlphaFold2 predicted models; (iii) newly predicted domain-domain interface annotations; (iv) an expanded in silico saturation mutagenesis incorporating 4 variant impact predictors; (v) a comprehensive overhaul of available data, including population data sources and variants reported pathogenic in the literature; (vi) A curated mapping of existing protein, transcript and chromosomal sequence positions and a new variant conversion tool to translate variants in one format to any other format. Availability and ImplementationDatabase accessible via titindb.kcl.ac.uk/TITINdb/ ContactFranca Fraternali (f.fraternali@ucl.ac.uk) Supplementary InformationAvailable