SomaMutDB 2.0: A comprehensive database for exploring somatic mutations and their functional impact in normal human tissues

Recent advances in ultra-accurate sequencing technologies have revealed that somatic mutations accumulate throughout the human lifespan and may contribute to both normal aging and disease. These mutations are highly diverse, often non-recurrent, and functionally heterogeneous, making their biological impact difficult to evaluate systematically. Although many studies have profiled somatic mutations in individual tissues or limited cohorts, a centralized and scalable platform that integrates discoveries and supports functional interpretation has been lacking. To address this gap, we present SomaMutDB 2.0 (https://somamutdb.org/SomaMutDB/), a substantially expanded database cataloging 8.9 million mutations (8.57 million SNVs and 0.29 million INDELs) from 10 852 samples of 607 human subjects across 47 studies. Beyond expanded data coverage, SomaMutDB 2.0 introduces a comprehensive functional annotation framework applying 22 predictive models spanning coding, regulatory, expression-based, and ensemble predictors to systematically assess mutational impact. Users can browse pre-annotated variants through an interactive interface or upload their own variants for real-time analysis. Notably, all results are contextualized against mutations from normal, non-diseased tissues in the database, enabling more meaningful interpretation than raw scores alone. Together, these advances establish SomaMutDB 2.0 as the most comprehensive resource currently available for characterizing somatic mosaicism and its functional impact on human health and aging.