annotate-it: a swiss-knife approach to annotation, analysis and interpretation of single nucleotide variation in human disease

the increasing size and complexity of exome/genome sequencing data requires new tools for clinical geneticists to discover disease-causing variants. bottlenecks in identifying the causative variation include poor cross-sample querying, constantly changing functional annotation and not considering existing knowledge concerning the phenotype. we describe a methodology that facilitates exploration of patient sequencing data towards identification of causal variants under different genetic hypotheses. annotate-it facilitates handling, analysis and interpretation of high-throughput single nucleotide variant data. we demonstrate our strategy using three case studies. annotate-it is freely available and test data are accessible to all users at http://www.annotate-it.org.