Hundreds of mutations to the broadly expressed LMNA gene cause disease primarily within cardiac, muscular, and adipose tissues (1). Tissue-specific pathogenesis arises when mutant protein dysfunction ...

The emergence of a chemical system capable of self-replication and evolution is a critical event in the origin of life. RNA polymerase ribozymes can replicate RNA, but their large size and structural ...

This editorial refers to ‘Automated patch clamp data improve variant classification and penetrance stratification for SCN5A–Brugada syndrome’, by M.J. O’Ne

Multiplexed assays of variant effect (MAVEs) systematically measure variant function but have been limited to cancer cell lines rather than disease-relevant cell types. We developed saturation genome ...

Meet the PI and team members of the Mosley Lab.

In this Review, Roden and co-workers describe how multiplexed assays of variant effects can be used for high-throughput functional assessment of nearly all coding variants in a target sequence to impr...

SOD1 variants cause the motor neuron disease amyotrophic lateral sclerosis. Axakova et al. functionally assay ∼86% of all possible SOD1 missense variants, producing a variant-effect map resource that ...

In this Review, Roden and co-workers describe how multiplexed assays of variant effects can be used for high-throughput functional assessment of nearly all coding variants in a target sequence to impr...

Background: Hypertrophic cardiomyopathy (HCM) is a genetically heterogeneous disorder primarily linked to rare variants in sarcomere genes, though recently certain non-sarcomeric genes have emerged as...

At the Clinical Atlas of Variant Effects meeting (CLAVE meeting, July 2024, Pittsburgh USA), we developed recommendations for a draft atlas that can be realized by 2030, with a focus on empowering gen...

About 30% of children with short stature do not have a definitive diagnosis, leading to extra testing and anxiety.

Computational methods for assessing the likely impacts of mutations, known as variant effect predictors (VEPs), are widely used in the assessment and interpretation of human genetic variation, as well...

A study of electronic health records (EHRs) from 1.8 million patients at Vanderbilt University Medical Center highlights the growing role of genetic testing in clinical medicine. The study demonstrate...

Recently, de novo variants in an 18 nucleotide region in the centre of RNU4-2 were shown to cause ReNU syndrome, a syndromic neurodevelopmental disorder (NDD) that is predicted to affect tens of thous...

Hypertrophic cardiomyopathy (HCM) is an inherited cardiac condition affecting ∼1 in 500 and exhibits marked genetic heterogeneity. Previously publishe…

Single-cell measurement of the Huntington’s disease-causing CAG repeat reveals that somatic expansion of this repeat drives pathological changes in neurons, providing insights into disease progression...

Howard et al. combine mechanistic deep mutational scanning, cryo-EM, and constant-pH molecular dynamics simulations to provide a holistic view of proton activation in human pH-sensitive GPCRs.