About TITINdb

TITINdb is a web application which integrates titin structure, sequence, isoform, variant and disease information.

Titin is the largest protein in the body, each titin molecule spanning half a muscle sarcomere, with the longest inferred complete (IC) isoform consisting of 35991 amino acids. Recently titin has emerged as an important disease gene, with variants associated with myopathies such as HCM, DCM and HMERF.

This application allows disease associated nsSNVs from the literature and population nsSNVs from the 1000 genomes project and gnomAD database to be visualised on structure. Additionally the impact these nsSNVs has been predicted computationally using both structure and sequence based methods.

A consistent numbering scheme for both titin domains and positions has been instigated, with all positions being mapped to the reference IC isoform. Users can easily translate between isoforms when searching by position. Titin domain boundaries have also been defined by integrating titin sequence and experimental information (see documentation for more details).

Titin is modular in structure consisting primarily of Ig and Fn3 domains as well as a single kinase domain. Users can select PDB structures to visualise domains where these are available. Where no crystal or NMR structures are available, homology models are provided. Additionally users can upload their own domain structures to visualise nsSNVs on.

The database can be queried in the following ways:

  • by domain name
  • by position
  • by refSNP (rs) ID
  • by disease

All structures and nsSNV information can be downloaded from the relevant pages.

When using this tool in publication, please cite Laddach, A., M. Gautel and F. Fraternali (2017). "TITINdb-a computational tool to assess titin's role as a disease gene." Bioinformatics 33(21): 3482-3485.

Any comments or suggestions are welcomed - please contact anna.laddach@kcl.ac.uk