In the past 20 years, we have witnessed tremendous advances in our ability to diagnose and
treat genetic diseases of the kidney caused by complement dysregulation. Staggering …

Gene discovery for Mendelian conditions (MCs) offers a direct path to understanding
genome function. Approaches based on next-generation sequencing applied at scale have …

The classification of genetic variants represents a major challenge in the post-genome era
by virtue of their extraordinary number and the complexities associated with ascribing a …

We used a machine learning approach to analyze the within-gene distribution of missense
variants observed in hereditary conditions and cancer. When applied to 840 genes from the …

Neurodevelopmental disorders (NDDs) are clinically and genetically heterogenous; many
such disorders are secondary to perturbation in brain development and/or function. The …

Primary defects in lung branching morphogenesis, resulting in neonatal lethal pulmonary
hypoplasias, are incompletely understood. To elucidate the pathogenetics of human lung …

Background: Spontaneous coronary artery dissection (SCAD) is a cause of acute coronary
syndrome that predominantly affects women. Its pathophysiology remains unclear but …

Members of a paralogous gene family in which variation in one gene is known to cause
disease are eight times more likely to also be associated with human disease. Recent …

Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is associated with congenital
absence of the uterus, cervix, and the upper part of the vagina; it is a sex-limited trait …

Precise interpretation of the effects of rare protein-truncating variants (PTVs) is important for
accurate determination of variant impact. Current methods for assessing the ability of PTVs …