ArticleHuman mutation2018
Scaling resolution of variant classification differences in ClinVar between 41 clinical laboratories through an outlier approach.
Article in Human mutation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
33 citing papers in PubMed.
- Automated reanalysis of genomic data for rare disease diagnostics at scale.Nature medicine · 2026Article
- Rapid Whole-Genome Sequencing in Critically Ill Infants and Children with Suspected, Undiagnosed Genetic Diseases: Evolution to a First-Tier Clinical Laboratory Test in the Era of Precision Medicine.Children (Basel, Switzerland) · 2025Review
- The Clinical Genome Resource (ClinGen): Advancing genomic knowledge through global curation.Genetics in medicine : official journal of the American College of Medical Genetics · 2025Article
- Interpretation and classification of FBN1 variants associated with Marfan syndrome: consensus recommendations from the Clinical Genome Resource's FBN1 variant curation expert panel.Genome medicine · 2024Article
- SpadaHC: a database to improve the classification of variants in hereditary cancer genes in the Spanish population.Database : the journal of biological databases and curation · 2024Article
- Recommendations for risk allele evidence curation, classification, and reporting from the ClinGen Low Penetrance/Risk Allele Working Group.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- The consequences of data dispersion in genomics: a comparative analysis of data sources for precision medicine.BMC medical informatics and decision making · 2023Article
- Nemaline myopathy: reclassification of previously reported variants according to ACMG guidelines, and report of novel genetic variants.European journal of human genetics : EJHG · 2023Article
- Clinical implications of conflicting variant interpretations in the cancer genetics clinic.Genetics in medicine : official journal of the American College of Medical Genetics · 2023Article
- 2022 Curt Stern Award: Advancing genomic medicine through collaboration and data sharing.American journal of human genetics · 2023Article
- Reasons and Resolutions for Inconsistent Variant Interpretation.Human mutation · 2023Review
- Assessment of an automated approach for variant interpretation in screening for monogenic disorders: A single-center study.Molecular genetics & genomic medicine · 2022Review
- Shariant platform: Enabling evidence sharing across Australian clinical genetic-testing laboratories to support variant interpretation.American journal of human genetics · 2022Review
- Harmonizing variant classification for return of results in the All of Us Research Program.Human mutation · 2022Article
- Reanalysis of eMERGE phase III sequence variants in 10,500 participants and infrastructure to support the automated return of knowledge updates.Genetics in medicine : official journal of the American College of Medical Genetics · 2022Article
- Adaptation of ACMG-ClinGen Technical Standards for Copy Number Variant Interpretation Concordance.Frontiers in genetics · 2022Article
- Article
- GA4GH: International policies and standards for data sharing across genomic research and healthcare.Cell genomics · 2021Article
- Scaling national and international improvement in virtual gene panel curation via a collaborative approach to discordance resolution.American journal of human genetics · 2021Review
- Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes.Nature communications · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors.
Funding
Abstract
ClinVar provides open access to variant classifications shared from many clinical laboratories. Although most classifications are consistent across laboratories, classification differences exist. To facilitate resolution of classification differences on a large scale, clinical laboratories were encouraged to reassess outlier classifications of variants with medically significant differences (MSDs). Outliers were identified by first comparing ClinVar submissions from 41 clinical laboratories to detect variants with MSDs between the laboratories (650 variants). Next, MSDs were filtered for variants with ≥3 classifications (244 variants), of which 87.6% (213 variants) had a majority consensus in ClinVar, thus allowing for identification of outlier classifications in need of reassessment. Laboratories with outlier classifications were sent a custom report and encouraged to reassess variants. Results were returned for 204 (96%) variants, of which 62.3% (127) were resolved. Of those 127, 64.6% (82) were resolved due to reassessment prompted by this study and 35.4% (45) resolved by a previously completed reassessment. This study demonstrates a scalable approach to classification resolution and capitalizes on the value of data sharing within ClinVar. These activities will help the community move toward more consistent variant classifications, which will improve the care of patients with, or at risk for, genetic disorders.
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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.