TITINdb2—expanding annotation and structural information for protein variants in the giant sarcomeric protein titin

• DOI: 10.1093/bioadv/vbaf062
• Publication Date: 2025-03-23T12:06:10Z
• Authors: Timir Weston; Joseph Ng; Oriol Gracia Carmona; Mathias Gautel; Franca Fraternali

Abstract

Summary We 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) through structural coverage of single domains with AlphaFold2 predicted models; (iii) newly predicted domain–domain interface annotations; (iv) an expanded in silico saturation mutagenesis incorporating four variant impact predictors; (v) a comprehensive overhaul of available data, including population data sources and variants reported pathogenic in the literature; and (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 implementation The database is accessible via titindb.kcl.ac.uk/TITINdb/.