ArticleAmerican journal of human genetics2018
A Multiplex Homology-Directed DNA Repair Assay Reveals the Impact of More Than 1,000 BRCA1 Missense Substitution Variants on Protein Function.
Article in American journal of human genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed.
- BCAR: a fast and indel-tolerant barcode-sequence mapper.Bioinformatics (Oxford, England) · 2026Article
- Assessing the Clinical Relevance ofCurrent oncology (Toronto, Ont.) · 2026Article
- Functional dissection ofProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Functional assays for BRCA1 and BRCA2 variant analysis: new tools and their applications.NPJ breast cancer · 2026Review
- BCAR: A fast and general barcode-sequence mapper for correcting sequencing errors.bioRxiv : the preprint server for biology · 2026Article
- Determining the intra-residue correlation of missense variant impact using MAVE scores: implications for the ACMG/AMP PM5 criterion for DNA variant classification.Genome medicine · 2026Article
- The functional landscape of coding variation in the familial hypercholesterolemia geneScience (New York, N.Y.) · 2026Article
- CodonMutator: a python-based automated oligonucleotide design framework for deep mutational scanning library construction.BMB reports · 2026Article
- Site-saturation functional screens identify PALB2 missense variants associated with increased breast cancer risk.Nature communications · 2026Article
- Functional assessment of protein variants in structured domains by fluorescence cross-correlation spectroscopy.Scientific reports · 2026Article
- Characterizing Variants of Uncertain Drug Resistance (VUDRs) Using Quantitative Measurements at Clinical Exposures.bioRxiv : the preprint server for biology · 2025Article
- Functional characterization of BRCA1 variants of unknown significance using homologous recombination repair assays.Breast cancer research : BCR · 2025Article
- Multiplex and multimodal mapping of variant effects in secreted proteins via MultiSTEP.Nature structural & molecular biology · 2025Article
- Article
- Gene-based calibration of high-throughput functional assays for clinical variant classification.bioRxiv : the preprint server for biology · 2025Article
- Variability in proliferative and migratory defects in Hirschsprung disease-associated RET pathogenic variants.American journal of human genetics · 2025Article
- Multiplex, multimodal mapping of variant effects in secreted proteins.bioRxiv : the preprint server for biology · 2025Article
- Reclassification of VUS inGenetics in medicine open · 2025Article
- Variability in proliferative and migratory defects in Hirschsprung disease-associatedbioRxiv : the preprint server for biology · 2024Article
- SIGMA leverages protein structural information to predict the pathogenicity of missense variants.Cell reports methods · 2024Article
22 more citing papers are in PubMed but not listed here.
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8 authors.
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Abstract
Loss-of-function pathogenic variants in BRCA1 confer a predisposition to breast and ovarian cancer. Genetic testing for sequence changes in BRCA1 frequently reveals a missense variant for which the impact on cancer risk and on the molecular function of BRCA1 is unknown. Functional BRCA1 is required for the homology-directed repair (HDR) of double-strand DNA breaks, a critical activity for maintaining genome integrity and tumor suppression. Here, we describe a multiplex HDR reporter assay for concurrently measuring the effects of hundreds of variants of BRCA1 for their role in DNA repair. Using this assay, we characterized the effects of 1,056 amino acid substitutions in the first 192 residues of BRCA1. Benchmarking these results against variants with known effects on DNA repair function or on cancer predisposition, we demonstrate accurate discrimination of loss-of-function versus benign missense variants. We anticipate that this assay can be used to functionally characterize BRCA1 missense variants at scale, even before the variants are observed in results from genetic testing.
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