ReviewAnnals of internal medicine2022
The Challenge of Genetic Variants of Uncertain Clinical Significance : A Narrative Review.
Review in Annals of internal medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers, 3 of them syntheses that pooled it.
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
120 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- How variants of uncertain significance affect clinical decisions: A systematic review.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Pooled it
- Yield of Whole Genome Sequencing for Pathogenic Single Nucleotide Variants in Congenital Heart Disease: A Systematic Review and Meta-Analysis.Prenatal diagnosis · 2026Pooled it
- What is the power of a genomic multidisciplinary team approach? A systematic review of implementation and sustainability.European journal of human genetics : EJHG · 2024Pooled it
- Outcomes of germ line testing for children with hematologic malignancies undergoing hematopoietic cell transplantation.Blood advances · 2026Article
- Probabilistic mapping of sub-genic intolerance reveals functional and disease-critical protein regions.bioRxiv : the preprint server for biology · 2026Article
- Targeted Therapy, Immunotherapy, and Molecular Testing in Advanced Solid Tumors: A Medicare Analysis.Cancer medicine · 2026Observational
- Genomic profiling of Mexican patients with B-cell precursor acute lymphoblastic leukemia reveals clinically significant somatic and potential germline variants.The journal of pathology. Clinical research · 2026Article
- Role and relevance of genetic testing in patients with kidney stones: a review from EAU Section of Endourology.Current opinion in urology · 2026Review
- Exploring the Melanoma and Pancreatic Cancer Phenotype of a PotentialJCO precision oncology · 2026Article
- Psychological Impact ofClinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2026Article
- Article
- When Lipid-Lowering Therapy Fails: Lessons From Functional Genomics and Precision Lipidology.JACC. Case reports · 2026Article
- Rapid resolution of variants of uncertain significance (VUS). A complementary role for zebrafish in the era of multi-million-dollar therapies.NPJ genomic medicine · 2026Article
- Structure-Based Network Analysis of AlphaFold Structure Predictions Identifies Putative Causative Variants of Inherited Retinal Disease.Investigative ophthalmology & visual science · 2026Article
- A comprehensive map of missense trafficking variants in rhodopsin and their response to pharmacologic correction.Science advances · 2026Article
- A case report of non-syndromic colonic ganglioneuroma in a patient with juvenile polyposis.JPGN reports · 2026Article
- Advances in Primary Mitochondrial Diseases: Diagnosis, Natural History Studies and Clinical Trials.Genes · 2026Review
- Assessing the Clinical Relevance ofCurrent oncology (Toronto, Ont.) · 2026Article
- 'Missing' disease-causing variants in Alport syndrome.Nature reviews. Nephrology · 2026Review
- Article
60 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
5 authors.
Funding
Abstract
Genomic tests expand diagnostic and screening opportunities but also identify genetic variants of uncertain clinical significance (VUSs). Only a minority of VUSs are likely to prove pathogenic when later reassessed, but resolution of the uncertainty is rarely timely. That uncertainty adds complexity to clinical decision making and can result in harms and costs to patients and the health care system, including the time-consuming analysis required to interpret a VUS and the potential for unnecessary treatment and adverse psychological effects. Current efforts to improve variant interpretation will help reduce the scope of the problem, but the high prevalence of rare and novel variants in the human genome points to VUSs as an ongoing challenge. Additional strategies can help mitigate the potential harms of VUSs, including testing protocols that limit identification or reporting of VUSs, subclassification of VUSs according to the likelihood of pathogenicity, routine family-based evaluation of variants, and enhanced counseling efforts. All involve tradeoffs, and the appropriate balance of measures is likely to vary for different test uses and clinical settings. Cross-specialty deliberation and public input could contribute to systematic and broadly supported policies for managing VUSs.
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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.