Genetic Variation in Clinical Cohorts

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Source: NEJM

Original: https://www.nejm.org/doi/full/10.1056/NEJMc2518638?af=R&rss=currentIssue...

Published: 2026-03-11T09:00:02Z

The study revealed a high rate of inaccuracy in the naming of genetic variants in clinical cohorts, which has real-world implications for diagnosis.[1] Every manuscript submitted to the journal Genetics in Medicine contained at least one error in gene or variant nomenclature.[1] These inaccuracies greatly reduce the likelihood of finding variants in the routine searches necessary to gather evidence for a diagnosis, which can lead to missed diagnosis.[1] Hospital geneticists rely on published evidence, but due to inconsistent nomenclature, they are often unable to find relevant information even when it exists.[1] Many geneticists use simpler but less precise nomenclature, which prevents databases such as ClinVar and the Leiden Open Variation Database (LOVD) and AI tools from identifying evidence.[1] An example is the long-term use of different systems for Factor V Leiden, which led to incorrect assessment of thrombosis risk and inappropriate treatment decisions.[1] Another case is the inconsistent reporting of CFTR gene variants in cystic fibrosis, which has caused errors in the assessment of carrier status and disease risk in couples counseling.[1] The results of the study are being incorporated into a new ACMG standard that sets minimum requirements for variant data in clinical reports, databases, and literature.[1]