ArticleGenetics in medicine : official journal of the American College of Medical Genetics2025
Calibration of additional computational tools expands ClinGen recommendation options for variant classification with PP3/BP4 criteria.
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 47 papers, 1 of them a synthesis 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
47 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The prevalence of pathogenic variants in the BMPR2 gene in patients with the idiopathic pulmonary arterial hypertension in the Russian population: sequencing data and meta-analysis.Respiratory research · 2025Pooled it
- Variant Class-Specific Phenotypes and Outcomes in Pediatric TBX4-Associated Pulmonary Hypertension.Pediatric pulmonology · 2026Article
- AlphaGenome Atlas:medRxiv : the preprint server for health sciences · 2026Article
- Review
- Automated patch clamp data improve variant classification and penetrance stratification for SCN5A-Brugada syndrome.European heart journal · 2026Article
- Prediction of human missense variant effects from functional evidence.Nature genetics · 2026Article
- Evaluation of BoostDM, a somatic variant prediction tool, for the interpretation of germline variants in hereditary cancer genes.European journal of human genetics : EJHG · 2026Article
- Elevated Hemoglobin AJournal of clinical laboratory analysis · 2026Article
- Prime Editing-Based Functional Characterization Supports a Likely Pathogenic Interpretation ofGenes · 2026Article
- Decoding variants of uncertain significance in systemic autoinflammatory diseases.Nature reviews. Rheumatology · 2026Review
- Association of Common Ancestry-Enriched Variants With Cardiomyopathy and Arrhythmias.Circulation · 2026Article
- Clinical characteristics and genetic features of patients with Wilson's disease in southwestern China.Orphanet journal of rare diseases · 2026Article
- Gene- and domain-aware calibration increases the clinical utility of variant effect predictors.Research square · 2026Article
- A novel compound heterozygosity in AAAS gene in two Greek siblings: expanding the genotypic landscape of Allgrove syndrome.Neurogenetics · 2026Article
- AI-driven integration of genomic and exposome data for cancer risk: the combined risk score (CRS).Human genomics · 2026Review
- Calibration of in-frame indel variant effect predictors for clinical variant classification.bioRxiv : the preprint server for biology · 2026Article
- ClinGen Bayesian-Framework-Guided Interpretation of Compound HeterozygousDiagnostics (Basel, Switzerland) · 2026Article
- Article
- Cancer genomic profiling predicts pathogenicity ofmedRxiv : the preprint server for health sciences · 2026Article
- Creating an atlas of variant effects to resolve variants of uncertain significance and guide cardiovascular medicine.Nature reviews. Cardiology · 2026Review
Corrections and comments
- Update of
Authors and funding
13 authors.
Funding
Abstract
purposeWe previously developed an approach to calibrate computational tools for clinical variant classification, updating recommendations for the reliable use of variant impact predictors to provide evidence strength up to Strong. A new generation of tools using distinctive approaches has since been released, and these methods must be independently calibrated for clinical application.
methodsUsing our local posterior probability-based calibration and our established data set of ClinVar pathogenic and benign variants, we determined the strength of evidence provided by 3 new tools (AlphaMissense, ESM1b, and VARITY) and calibrated scores meeting each evidence strength.
resultsAll 3 tools reached the Strong level of evidence for variant pathogenicity and Moderate for benignity, although sometimes for few variants. Compared with previously recommended tools, these yielded at best only modest improvements in the trade-offs between evidence strength and false-positive predictions.
conclusionAt calibrated thresholds, 3 new computational predictors provided evidence for variant pathogenicity at similar strength to the 4 previously recommended predictors (and comparable with functional assays for some variants). This calibration broadens the scope of computational tools for application in clinical variant classification. Their new approaches offer promise for future advancement of the field.
Indexed as
Identifiers
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.