ArticleMolecular cell2019
A Multiplexed Assay for Exon Recognition Reveals that an Unappreciated Fraction of Rare Genetic Variants Cause Large-Effect Splicing Disruptions.
Article in Molecular cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
90 citing papers in PubMed.
- Interpretable distillation reveals that deep learning splicing models suffer from pervasive confounders and blind spots.Genome biology · 2026Article
- Uncultured Amniocytes Enable Rapid and Clinically Informative Prenatal RNA Sequencing for Genetic Diagnosis.International journal of molecular sciences · 2026Article
- Update of germ line RUNX1 variant curation rules: version 3.1.Blood advances · 2026Article
- Improving splice site usage prediction with SPLAIRE.bioRxiv : the preprint server for biology · 2026Article
- Comprehensive review and assessment of multi-species splicing variant prediction: task-specific deep learning models and genomic foundation models.Briefings in bioinformatics · 2026Review
- RNA Sequencing Resolves Cryptic Pathogenic Variants in Mitochondrial Disease.Annals of clinical and translational neurology · 2026Article
- The conundrum in diagnosing Maturity-Onset Diabetes of the Young (MODY) in a large German pedigree with early-onset diabetes and a novel HNF1A variant.Molecular and cellular pediatrics · 2026Article
- Utility of Targeted RNA Analysis in Neurogenetic Disorders.Neurology. Genetics · 2026Article
- Protocol for validating computationally predicted splice-altering variants using full-length gene reporter assays.STAR protocols · 2026Article
- Multiplexed assays of variant effect for clinical variant interpretation.Nature reviews. Genetics · 2026Review
- High-Throughput Methods for Variant Functional Assessment in Cardiac Disease.Circulation. Genomic and precision medicine · 2026Review
- Benchmarking RNA-seq Tools for Real-World Diagnostic Applications.Research square · 2026Article
- Benchmarking RNA-seq Tools for Real-World Diagnostic Applications.medRxiv : the preprint server for health sciences · 2026Article
- Article
- RNA-guided clarity: The potential for resolving variant uncertainty in clinical exome sequencing.Genetics in medicine open · 2026Article
- Article
- Synonymous and non-synonymous variants at splice junctions can disrupt splicing and are frequently linked to disease associated loss of function genes.BMC genomics · 2025Article
- Generative Design of Cell Type-Specific RNA Splicing Elements for Programmable Gene Regulation.bioRxiv : the preprint server for biology · 2025Article
- Long-read RNA-seq demarcates cis- and trans-directed alternative RNA splicing.Nature communications · 2025Article
- SpliPath enhances disease gene discovery in case-control analyses of rare splice-altering genetic variants.Cell reports methods · 2025Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
Mutations that lead to splicing defects can have severe consequences on gene function and cause disease. Here, we explore how human genetic variation affects exon recognition by developing a multiplexed functional assay of splicing using Sort-seq (MFASS). We assayed 27,733 variants in the Exome Aggregation Consortium (ExAC) within or adjacent to 2,198 human exons in the MFASS minigene reporter and found that 3.8% (1,050) of variants, most of which are extremely rare, led to large-effect splice-disrupting variants (SDVs). Importantly, we find that 83% of SDVs are located outside of canonical splice sites, are distributed evenly across distinct exonic and intronic regions, and are difficult to predict a priori. Our results indicate extant, rare genetic variants can have large functional effects on splicing at appreciable rates, even outside the context of disease, and MFASS enables their empirical assessment at scale.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.