Understanding the consequences of genotype for phenotype (which ranges from molecule-
level effects to whole-organism traits) is at the core of genetic diagnostics in medicine. Many …

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 …

Genome sequencing in the clinic often allows patients to receive a molecular diagnosis.
However, variants are most often evaluated for pathogenicity, neglecting potential treatability …

The incidence of adenocarcinoma of the esophagogastric junction (AEG) has been rapidly
increasing in recent decades, but its molecular alterations and subtypes are still obscure …

Clarkson disease, or monoclonal gammopathy–associated idiopathic systemic capillary leak
syndrome (ISCLS), is a rare, relapsing-remitting disorder featuring the abrupt extravasation …

Most published studies identify groundwater extraction as the leading cause of land
subsidence (LS). However, the causes of LS are not only attributable to groundwater …

Predicting pathogenicity of missense variants in molecular diagnostics remains a challenge
despite the available wealth of data, such as evolutionary information, and the wealth of …

Mutations in human proteins lead to diseases. The structure of these proteins can help
understand the mechanism of such diseases and develop therapeutics against them. With …

Determining the pathogenicity and functional impact (ie gain-of-function; GOF or loss-of-
function; LOF) of a variant is vital for unraveling the genetic level mechanisms of human …

Inborn errors of immunity lead to autoimmunity, inflammation, allergy, infection, and/or
malignancy. Disease-causing JAK1 gain-of-function (GoF) mutations are considered …