Genetic variations resulting in a change of amino acid sequence can have a dramatic effect
on stability, hydrogen bond network, conformational dynamics, activity and many other …

Most known pathogenic mutations occur in protein-coding regions of DNA and change the
way proteins are made. Taking protein structure into account has therefore provided great …

Cancer is often driven by the accumulation of genetic alterations, including single nucleotide
variants, small insertions or deletions, gene fusions, copy-number variations, and large …

Motivation: Gain-of-function mutations often cluster in specific protein regions, a signal that
those mutations provide an adaptive advantage to cancer cells and consequently are …

Large-scale tumor sequencing projects enabled the identification of many new cancer gene
candidates through computational approaches. Here, we describe a general method to …

Quantification of the tolerance of protein sites to genetic variation has become a cornerstone
of variant interpretation. We hypothesize that the constraint on missense variation at …

Haploinsufficiency (HI) is the best characterized mechanism through which dominant
mutations exert their effect and cause disease. Non-haploinsufficiency (NHI) mechanisms …

Identifying driver mutations in cancer is notoriously difficult. To date, recurrence of a mutation
in patients remains one of the most reliable markers of mutation driver status. However …

Precision cancer medicine promises to tailor clinical decisions to patients using genomic
information. Indeed, successes of drugs targeting genetic alterations in tumors, such as …

Variations and similarities in our individual genomes are part of our history, our heritage,
and our identity. Some human genomic variants are associated with common traits such as …