ArticleNature2018
Accurate classification of BRCA1 variants with saturation genome editing.
Article in Nature, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 547 papers.
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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.
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Who cites it
547 citing papers in PubMed.
- Genetic kidney diseases: Decoding molecular taxonomies to drive precision nephrology and therapeutic innovation.Genes & diseases · 2027Review
- cPRIME enables endogenous mapping of genetic variant effects at RNA level.Nature communications · 2026Article
- AlphaGenome Atlas:medRxiv : the preprint server for health sciences · 2026Article
- Probabilistic mapping of sub-genic intolerance reveals functional and disease-critical protein regions.bioRxiv : the preprint server for biology · 2026Article
- Minigene-based characterization and classification of splice-associated variants in succinate dehydrogenase B.NPJ precision oncology · 2026Article
- CRISPRing through time: How cutting-edge technology is revolutionizing life sciences and medicine.Molecular therapy. Nucleic acids · 2026Review
- Large serine recombinase-mediated gene insertion for high-throughput screens: advantages, design principles, and applications.Nucleic acids research · 2026Review
- Induced pluripotent stem cells from discovery to translation.Nature medicine · 2026Review
- Hereditary diffuse gastric cancer in progress: Comparative lessons from Lynch syndrome.European journal of human genetics : EJHG · 2026Review
- Validation structures for sequence variants of uncertain significance in hereditary cancer.European journal of human genetics : EJHG · 2026Review
- Reclassification ofCurrent oncology (Toronto, Ont.) · 2026Article
- Donor-complementary prime editing enables precise kilobase and library-compatible DNA insertions.Nature biotechnology · 2026Article
- Why variant effect predictors and multiplexed assays agree and disagree.Nature communications · 2026Article
- Deciphering protein mutation-phenotype linkages from CRISPR-based tiling mutagenesis screens.Cell systems · 2026Article
- Likelihood-based calibration improves the clinical utility of JAG1 functional data for variant classification.American journal of human genetics · 2026Article
- Global patterns of mutational profiles in biliary tract cancer.Journal of hepatology · 2026Article
- A prioritization framework for BRCA1/2 variants of uncertain significance identified by comprehensive genomic profiling.European journal of human genetics : EJHG · 2026Article
- A comprehensive map of missense trafficking variants in rhodopsin and their response to pharmacologic correction.Science advances · 2026Article
- 'Truthsets' for clinical validation of large-scale functional assays: Practice recommendations from Cancer Variant Interpretation Group UK (CanVIG-UK).medRxiv : the preprint server for health sciences · 2026Article
- Scaled Multidimensional Assays of Variant Effect Identify Sequence-Function Relationships in Hypertrophic Cardiomyopathy.Circulation · 2026Article
487 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors.
Funding
Abstract
Variants of uncertain significance fundamentally limit the clinical utility of genetic information. The challenge they pose is epitomized by BRCA1, a tumour suppressor gene in which germline loss-of-function variants predispose women to breast and ovarian cancer. Although BRCA1 has been sequenced in millions of women, the risk associated with most newly observed variants cannot be definitively assigned. Here we use saturation genome editing to assay 96.5% of all possible single-nucleotide variants (SNVs) in 13 exons that encode functionally critical domains of BRCA1. Functional effects for nearly 4,000 SNVs are bimodally distributed and almost perfectly concordant with established assessments of pathogenicity. Over 400 non-functional missense SNVs are identified, as well as around 300 SNVs that disrupt expression. We predict that these results will be immediately useful for the clinical interpretation of BRCA1 variants, and that this approach can be extended to overcome the challenge of variants of uncertain significance in additional clinically actionable genes.
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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.