AUTHOR=Licata Luana , Via Allegra , Turina Paola , Babbi Giulia , Benevenuta Silvia , Carta Claudio , Casadio Rita , Cicconardi Andrea , Facchiano Angelo , Fariselli Piero , Giordano Deborah , Isidori Federica , Marabotti Anna , Martelli Pier Luigi , Pascarella Stefano , Pinelli Michele , Pippucci Tommaso , Russo Roberta , Savojardo Castrense , Scafuri Bernardina , Valeriani Lucrezia , Capriotti Emidio TITLE=Resources and tools for rare disease variant interpretation JOURNAL=Frontiers in Molecular Biosciences VOLUME=10 YEAR=2023 URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2023.1169109 DOI=10.3389/fmolb.2023.1169109 ISSN=2296-889X ABSTRACT=

Collectively, rare genetic disorders affect a substantial portion of the world’s population. In most cases, those affected face difficulties in receiving a clinical diagnosis and genetic characterization. The understanding of the molecular mechanisms of these diseases and the development of therapeutic treatments for patients are also challenging. However, the application of recent advancements in genome sequencing/analysis technologies and computer-aided tools for predicting phenotype-genotype associations can bring significant benefits to this field. In this review, we highlight the most relevant online resources and computational tools for genome interpretation that can enhance the diagnosis, clinical management, and development of treatments for rare disorders. Our focus is on resources for interpreting single nucleotide variants. Additionally, we present use cases for interpreting genetic variants in clinical settings and review the limitations of these results and prediction tools. Finally, we have compiled a curated set of core resources and tools for analyzing rare disease genomes. Such resources and tools can be utilized to develop standardized protocols that will enhance the accuracy and effectiveness of rare disease diagnosis.