ArticleGenetics in medicine : official journal of the American College of Medical Genetics2025
Distinct rates of VUS reclassification are observed when subclassifying VUS by evidence level.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Overview of next-generation sequencing to the molecular diagnosis of inborn errors of immunity in Brazil: a systematic review.Frontiers in immunology · 2026Pooled it
- Making Genomic Data Actionable in Electronic Health Records: Practical Viewpoint on Standards, Governance, and Implementation.JMIR medical informatics · 2026Article
- Improving Severe Combined Immunodeficiency and Cystic Fibrosis Newborn Screening by Replacing Current Tests with First-Tier Targeted Gene Sequencing.International journal of neonatal screening · 2026Article
- A comparative survey of functional evidence use in hearing and vision loss genetics.Communications medicine · 2026Article
- From text to translation: using language models to prioritize variants for clinical review.Genome medicine · 2026Article
- Benchmarking genetic birth prevalence estimates against newborn screening data.American journal of human genetics · 2026Article
- Gene-related retinal detachment in a young Chinese cohort: ACMG/AMP applicability and VUS analysis.International journal of ophthalmology · 2026Article
- A case report in hypertrophic cardiomyopathy in a recreational athlete: multimodality risk assessment, genetic insights, and shared decision-making.European heart journal. Case reports · 2026Article
- Not "just a VUS".Genetics in medicine open · 2026Article
- Toward universal screening for disease-causing alleles: Mendelian susceptibility to mycobacterial disease as a model.Journal of human immunity · 2025Review
- Deep Mutational Scanning in Immunology: Techniques and Applications.Pathogens (Basel, Switzerland) · 2025Review
- Mosaic X-linked adrenoleukodystrophy in males identified by newborn screening and next-generation sequencing.NPJ genomic medicine · 2025Article
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9 authors.
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Abstract
purposeGenetic testing commonly yields a plethora of variants of uncertain significance (VUS) that can lead to ongoing uncertainty for patients and their caregivers. Although all VUS hold uncertainty, some VUS have more evidence in support of pathogenicity, whereas others have more evidence of a benign role. Sharing these nuances can help guide the investment in follow-up clinical and research investigations and may, at times, influence medical decision making despite appreciated uncertainty.
methodsFour clinical laboratories have been subclassifying VUS to help prioritize investigation and guide reporting decisions. Each laboratory developed a distinct approach for how these subclasses are used in their laboratories and, in some cases, displayed on reports. We examined the composition of each laboratory's VUS subclasses and the likelihood variants from each subclass were reclassified toward pathogenic or benign.
resultsWe found that variants in the lowest subclass of VUS were never reclassified as likely pathogenic or pathogenic, whereas those in the highest subclass were much more likely to be reclassified as pathogenic or likely pathogenic.
conclusionGiven that forthcoming professional guidance in variant classification will advise the use of VUS subclasses, the experience of our laboratories in using VUS subclasses can inform future practices.
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