ArticleGenetics in medicine : official journal of the American College of Medical Genetics2023
The landscape of reported VUS in multi-gene panel and genomic testing: Time for a change.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 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.
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.
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Who cites it
75 citing papers in PubMed, 121 citations in OpenAlex.
- Interpreting human genetic variation at atomic resolution.Nature genetics · 2026Review
- Prediction of human missense variant effects from functional evidence.Nature genetics · 2026Article
- Decoding variants of uncertain significance in systemic autoinflammatory diseases.Nature reviews. Rheumatology · 2026Review
- Variant-specific RNA testing resolves variants of uncertain significance in exome testing.BMC genomics · 2026Article
- Article
- From variants to answers: The evolution of genetic counseling in IEI.Journal of human immunity · 2026Review
- Pathways to enhancing prenatal diagnosis of skeletal dysplasias.Pregnancy (Hoboken, N.J.) · 2026Review
- Utility of Targeted RNA Analysis in Neurogenetic Disorders.Neurology. Genetics · 2026Article
- Spectrum of dominant Charcot-Marie-Tooth disease due toJournal of neurology, neurosurgery, and psychiatry · 2026Article
- Identification of de novo variants from parent-proband duos via long-read sequencing.American journal of human genetics · 2026Article
- Advantages of Exome Sequencing Over Panel Testing for Individuals With a Seizure Indication.Annals of the Child Neurology Society · 2026Article
- Diagnostic yield of exome and genome sequencing for critically ill pediatric cardiac patients.Translational pediatrics · 2026Article
- Subtle cellular phenotypes inform pathological and benign genetic mutants in the Iduronate-2 sulfatase gene.Human molecular genetics · 2026Article
- Multiplexed assays of variant effect for clinical variant interpretation.Nature reviews. Genetics · 2026Review
- Not "just a VUS".Genetics in medicine open · 2026Article
- Gene-related retinal detachment in a young Chinese cohort: ACMG/AMP applicability and VUS analysis.International journal of ophthalmology · 2026Article
- Functional analysis of AIP variants in a cohort of neuroendocrine neoplasms.Endocrine-related cancer · 2026Article
- Spectrum and carrier frequency of DMD in Yueyang, China: a population-based analysis using NGS and MLPA.Frontiers in genetics · 2026Article
- Rapid targeted analysis of the genome: Rapid genomic sequencing in critically ill infants.Genetics in medicine open · 2026Article
- Yield of actionable variants from high-risk cancer gene panel testing in guideline-eligible and ineligible individuals.Frontiers in genetics · 2026Article
15 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
63 authors at 20 institutions in 2 countries.
Funding
Abstract
purposeVariants of uncertain significance (VUS) are a common result of diagnostic genetic testing and can be difficult to manage with potential misinterpretation and downstream costs, including time investment by clinicians. We investigated the rate of VUS reported on diagnostic testing via multi-gene panels (MGPs) and exome and genome sequencing (ES/GS) to measure the magnitude of uncertain results and explore ways to reduce their potentially detrimental impact.
methodsRates of inconclusive results due to VUS were collected from over 1.5 million sequencing test results from 19 clinical laboratories in North America from 2020 to 2021.
resultsWe found a lower rate of inconclusive test results due to VUSs from ES/GS (22.5%) compared with MGPs (32.6%; P < .0001). For MGPs, the rate of inconclusive results correlated with panel size. The use of trios reduced inconclusive rates (18.9% vs 27.6%; P < .0001), whereas the use of GS compared with ES had no impact (22.2% vs 22.6%; P = ns).
conclusionThe high rate of VUS observed in diagnostic MGP testing warrants examining current variant reporting practices. We propose several approaches to reduce reported VUS rates, while directing clinician resources toward important VUS follow-up.
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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.