Nicola Whiffin

TL;DR: A catalogue of predicted loss-of-function variants in 125,748 whole-exome and 15,708 whole-genome sequencing datasets from the Genome Aggregation Database (gnomAD) reveals the spectrum of mutational constraints that affect these human protein-coding genes.

TL;DR: Using an improved human mutation rate model, human protein-coding genes are classified along a spectrum representing tolerance to inactivation, validate this classification using data from model organisms and engineered human cells, and show that it can be used to improve gene discovery power for both common and rare diseases.

TL;DR: A statistically robust framework for assessing whether a variant is “too common” to be causative for a Mendelian disorder of interest is outlined and precomputed allele frequency cutoffs for all variants in the ExAC dataset are presented.

TL;DR: Many patients deemed to have recovered from dilated cardiomyopathy will relapse following treatment withdrawal, and until robust predictors of relapse are defined, treatment should continue indefinitely.

TL;DR: These adapted rules provide increased specificity for use in MYH7-associated disorders in combination with expert review and clinical judgment and serve as a stepping stone for genes and disorders with similar genetic and clinical characteristics.