ArticleJournal of medical genetics2022
Data sharing to improve concordance in variant interpretation across laboratories: results from the Canadian Open Genetics Repository.
Article in Journal of medical genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Critical Role of Molecular-Based Stratification in Low-Risk Myelodysplastic Syndrome with Direct Progression to Acute Myeloid Leukemia: A Case Report.International journal of molecular sciences · 2026Article
- A Novel Frameshift Mutation inBiomedicines · 2026Article
- MaveMD: A functional data resource for genomic medicine.medRxiv : the preprint server for health sciences · 2025Article
- Comorbidities in Mild WAS/XLT Require Lifelong Follow-Up and Consideration of Definitive Treatment.American journal of hematology · 2025Article
- Investigating the frequency of unreported cases and laboratory correspondence practices for variants of uncertain significance in pediatric epilepsy.Epilepsia open · 2025Article
- Germline genetic variants in young-onset sporadic pituitary macroadenomas: A multigene panel analysis.Journal of clinical & translational endocrinology · 2025Article
- Genetic analysis of 25 Chinese pedigrees with neurofibromatosis type 1 and genotype-phenotype study from an extended cohort.Orphanet journal of rare diseases · 2025Article
- 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
- Canadian College of Medical Geneticists: clinical practice advisory document - responsibility to recontact for reinterpretation of clinical genetic testing.Journal of medical genetics · 2024Article
- State of open science in cancer research.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 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
- The expanding diagnostic toolbox for rare genetic diseases.Nature reviews. Genetics · 2024Review
- Improvement of variant reclassification in genetic neurodevelopmental conditions.Genetics in medicine open · 2024Article
- Shariant platform: Enabling evidence sharing across Australian clinical genetic-testing laboratories to support variant interpretation.American journal of human genetics · 2022Review
- BRCA1 Norway: comparison of classification for BRCA1 germline variants detected in families with suspected hereditary breast and ovarian cancer between different laboratories.Familial cancer · 2022Article
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- Review
- From the patient to the population: Use of genomics for population screening.Frontiers in genetics · 2022Article
- Article
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Authors and funding
34 authors.
Funding
Abstract
backgroundThis study aimed to identify and resolve discordant variant interpretations across clinical molecular genetic laboratories through the Canadian Open Genetics Repository (COGR), an online collaborative effort for variant sharing and interpretation.
methodsLaboratories uploaded variant data to the Franklin Genoox platform. Reports were issued to each laboratory, summarising variants where conflicting classifications with another laboratory were noted. Laboratories could then reassess variants to resolve discordances. Discordance was calculated using a five-tier model (pathogenic (P), likely pathogenic (LP), variant of uncertain significance (VUS), likely benign (LB), benign (B)), a three-tier model (LP/P are positive, VUS are inconclusive, LB/B are negative) and a two-tier model (LP/P are clinically actionable, VUS/LB/B are not). We compared the COGR classifications to automated classifications generated by Franklin.
resultsTwelve laboratories submitted classifications for 44 510 unique variants. 2419 variants (5.4%) were classified by two or more laboratories. From baseline to after reassessment, the number of discordant variants decreased from 833 (34.4% of variants reported by two or more laboratories) to 723 (29.9%) based on the five-tier model, 403 (16.7%) to 279 (11.5%) based on the three-tier model and 77 (3.2%) to 37 (1.5%) based on the two-tier model. Compared with the COGR classification, the automated Franklin classifications had 94.5% sensitivity and 96.6% specificity for identifying actionable (P or LP) variants.
conclusionsThe COGR provides a standardised mechanism for laboratories to identify discordant variant interpretations and reduce discordance in genetic test result delivery. Such quality assurance programmes are important as genetic testing is implemented more widely in clinical care.
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