ReviewHuman mutation2012
A review of a multifactorial probability-based model for classification of BRCA1 and BRCA2 variants of uncertain significance (VUS).
Review in Human mutation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers.
What it found
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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
138 citing papers in PubMed, 246 citations in OpenAlex.
- Functional characterization of BRCA2 variants of uncertain significance identified in Korean breast cancer patients.Breast cancer (Tokyo, Japan) · 2026Article
- Evaluation of non-canonical p53 functions in DNA replication and recombination for variant classification.Cell death & disease · 2026Article
- Functional assessment of protein variants in structured domains by fluorescence cross-correlation spectroscopy.Scientific reports · 2026Article
- Clinical variant interpretation comparing two saturation genome editing-based functional studies forFrontiers in genetics · 2026Article
- Availability of benign missense variant "truthsets" for validation of functional assays: Current status and a systematic approach.American journal of human genetics · 2025Article
- Hereditary breast and ovarian cancer genetic testing in unselected patients: example of private supplementation of public healthcare service.Familial cancer · 2024Article
- Co-observation of germline pathogenic variants in breast cancer predisposition genes: Results from analysis of the BRIDGES sequencing dataset.American journal of human genetics · 2024Article
- Evidence-based recommendations for gene-specific ACMG/AMP variant classification from the ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel.American journal of human genetics · 2024Article
- Rare Germline Variants in DNA Repair Genes Detected inCancers · 2024Article
- Functional Characterization of the Human BRCA1 ∆11 Splicing Isoforms in Yeast.International journal of molecular sciences · 2024Article
- Functional analysis and clinical classification of 462 germline BRCA2 missense variants affecting the DNA binding domain.American journal of human genetics · 2024Article
- Classification of MLH1 Missense VUS Using Protein Structure-Based Deep Learning-Ramachandran Plot-Molecular Dynamics Simulations Method.International journal of molecular sciences · 2024Article
- Male with an apparently normal phenotype carrying a BRCA1 exon 20 duplication in trans to a BRCA1 frameshift variant.Breast cancer research : BCR · 2024Article
- Long-term outcomes of young, node-negative, chemotherapy-naïve, triple-negative breast cancer patients according to BRCA1 status.BMC medicine · 2024Article
- Primary Prevention and Early Detection of Hereditary Breast Cancer.Breast care (Basel, Switzerland) · 2023Review
- Article
- Diagnostic yield and clinical relevance of expanded germline genetic testing for nearly 7000 suspected HBOC patients.European journal of human genetics : EJHG · 2023Article
- The pathogenic role of the BRCA2 c.7847C>T (p.Ser2616Phe) variant in breast and ovarian cancer predisposition.Cancer science · 2023Article
- Ovarian cancer pathology characteristics as predictors of variant pathogenicity in BRCA1 and BRCA2.British journal of cancer · 2023Article
- Integration of deep learning with Ramachandran plot molecular dynamics simulation for genetic variant classification.iScience · 2023Article
78 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
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Clinical mutation screening of the BRCA1 and BRCA2 genes for the presence of germline inactivating mutations is used to identify individuals at elevated risk of breast and ovarian cancer. Variants identified during screening are usually classified as pathogenic (increased risk of cancer) or not pathogenic (no increased risk of cancer). However, a significant proportion of genetic tests yields variants of uncertain significance (VUS) that have undefined risk of cancer. Individuals carrying these VUS cannot benefit from individualized cancer risk assessment. Recently, a quantitative "posterior probability model" for assessing the clinical relevance of VUS in BRCA1 or BRCA2, which integrates multiple forms of genetic evidence has been developed. Here, we provide a detailed review of this model. We describe the components of the model and explain how these can be combined to calculate a posterior probability of pathogenicity for each VUS. We explain how the model can be applied to public data and provide tables that list the VUS that have been classified as not pathogenic or pathogenic using this method. While we use BRCA1 and BRCA2 VUS as examples, the method can be used as a framework for classification of the pathogenicity of VUS in other cancer genes.
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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.