Given the constantly improving cost and speed of genome sequencing, it is reasonable to
expect that personal genomes will soon be known for many millions of humans. This stands …

Sequencing has revealed hundreds of millions of human genetic variants, and continued
efforts will only add to this variant avalanche. Insufficient information exists to interpret the …

Classical genetic approaches for interpreting variants, such as case-control or co-
segregation studies, require finding many individuals with each variant. Because the …

Over the next decade, the primary challenge in human genetics will be to understand the
biological mechanisms by which genetic variants influence phenotypes, including disease …

New technologies have recently enabled saturation mutagenesis and functional analysis of
nearly all possible variants of regulatory elements or proteins of interest in single …

Variants of uncertain significance represent a massive challenge to medical genetics.
Multiplexed functional assays, in which the functional effects of thousands of genomic …

Background Genetic variant effect prediction algorithms are used extensively in clinical
genomics and research to determine the likely consequences of amino acid substitutions on …

Scalable sequence–function studies have enabled the systematic analysis and cataloging of
hundreds of thousands of coding and noncoding genetic variants in the human genome …

Multiplex assays of variant effect (MAVEs), such as deep mutational scans and massively
parallel reporter assays, test thousands of sequence variants in a single experiment. Despite …

The integrative analysis of high‐throughput reporter assays, machine learning, and profiles
of epigenomic chromatin state in a broad array of cells and tissues has the potential to …