ArticleGenetics in medicine : official journal of the American College of Medical Genetics2017
Sources of discordance among germ-line variant classifications in ClinVar.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 58 papers.
What it found
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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
58 citing papers in PubMed.
- Genome region aware CADD thresholds for noncoding variant prioritization.NAR genomics and bioinformatics · 2025Article
- Functional Profiling ofCirculation. Genomic and precision medicine · 2025Article
- Investigating the frequency of unreported cases and laboratory correspondence practices for variants of uncertain significance in pediatric epilepsy.Epilepsia open · 2025Article
- Using large-scale population-based data to improve disease risk assessment of clinical variants.Nature genetics · 2025Review
- Genetic disease risks of under-represented founder populations in New York City.PLoS genetics · 2025Article
- Meta-EA: a gene-specific combination of available computational tools for predicting missense variant effects.Nature communications · 2025Article
- Article
- Multi-Institutional Evaluation of Interrater Agreement of Biomarker-Drug Pair Rankings Based on the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) and Sources of Discordance.Molecular diagnosis & therapy · 2025Article
- Reinterpretation of Conflicting ClinVarDiagnostics (Basel, Switzerland) · 2024Article
- Major Causes of Conflicting Interpretations of Variant Pathogenicity in Rare Disease: A Systematic Analysis.Journal of personalized medicine · 2024Article
- Accuracy of renovo predictions on variants reclassified over time.Journal of translational medicine · 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
- An overview of actionable and potentially actionable TSC1 and TSC2 germline variants in an online Database.Genetics and molecular biology · 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
- Challenging interpretation of germline TP53 variants based on the experience of a national comprehensive cancer centre.Scientific reports · 2023Article
- ClinVar and HGMD genomic variant classification accuracy has improved over time, as measured by implied disease burden.Genome medicine · 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
- Variant curation and interpretation in hereditary cancer genes: An institutional experience in Latin America.Molecular genetics & genomic medicine · 2023Article
- Reasons and Resolutions for Inconsistent Variant Interpretation.Human mutation · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PurposeClinVar is increasingly used as a resource for both genetic variant interpretation and clinical practice. However, controversies exist regarding the consistency of classifications in ClinVar, and questions remain about how best to use these data. Our study systematically examined ClinVar to identify common sources of discordance and thus inform ongoing practices.MethodsWe analyzed variants that had multiple classifications in ClinVar, excluding benign polymorphisms. Classifications were categorized by potential actionability and pathogenicity. Consensus interpretations were calculated for each variant, and the properties of the discordant outlier classifications were summarized.ResultsOur study included 74,065 classifications of 27,224 unique variants in 1,713 genes. We found that (i) concordance rates differed among clinical areas and variant types; (ii) clinical testing methods had much higher concordance than basic literature curation and research efforts; (iii) older classifications had greater discordance than newer ones; and (iv) low-penetrance variants had particularly high discordance.ConclusionRecent variant classifications from clinical testing laboratories have high overall concordance in many (but not all) clinical areas. ClinVar can be a reliable resource supporting variant interpretation, quality assessment, and clinical practice when factors uncovered in this study are taken into account. Ongoing improvements to ClinVar may make it easier to use, particularly for nonexpert users.
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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.