Study Reveals Widespread Errors in Gene Variant Naming

Accurate variant nomenclature underpins the ability of clinical laboratories to retrieve and interpret evidence for rare disease diagnosis. Yet many patients face prolonged diagnostic journeys; in the U.K., about 6,000 children each year have rare genetic diseases, and around 70% remain undiagnosed. Inconsistent gene and variant naming has been linked to documented errors in clinical management and increased costs. New research now shows that imprecision in variant nomenclature is widespread across journal manuscript submissions.

A research team led by the University of Manchester conducted a systematic review of 52 papers submitted over two years to Genetics in Medicine, identifying nomenclature errors in every manuscript. The analysis, published in Clinical Chemistry on March 7, 2026, found that imprecision significantly reduces the likelihood of locating variants during routine literature searches for diagnostic evidence. The authors note that when evidence cannot be retrieved due to poor findability, diagnoses may be missed.

To improve consistency, the researchers created a tool called VariantValidator, which assigns each variant a standardized name to facilitate sharing and retrieval of diagnostic evidence. Working with the Human Genome Organization and the editors of Genetics in Medicine—the journal of the American College of Medical Genetics and Genomics (ACMG), which develops global professional standards in clinical genomics—they developed author instructions on proper variant reporting. 

The work is being incorporated into a new ACMG‑led professional standard with major professional societies and quality‑assurance bodies across the U.S., European Union, U.K., and Canada, to be announced later this year. Related standards have been legally binding in the United States, while U.K. adoption has not been indicated; however, U.K. quality bodies are part of the ACMG‑led coalition.

Miscommunication from inconsistent naming has led to incorrect clinical management. Longstanding discrepancies around the Factor V Leiden variant resulted in misinterpretation of thrombosis risk and inappropriate treatments, and inconsistent reporting of CFTR variants in cystic fibrosis contributed to misunderstandings of carrier status and disease risk, affecting family‑planning counseling. 

The study's authors recommend universal adoption of nomenclature guidelines in publications, implementation of robust peer-review processes to enforce gene and variant standards, automated submission of structured variant and classification data to public repositories, and closer collaboration with publishers to educate production and copyediting teams.

“The language of genomics, which guides everything from discoveries of gene-disease associations to rare disease diagnosis, relies on an established standardized system of naming genomic variants,” said Dr. Peter Freeman, geneticist at The University of Manchester and the study's lead author. "This study has revealed a shocking level of inaccuracy in the naming of genetic variants—which has real-world consequences. My team and I have yet to find a journal article which uses the correct nomenclature and did not require intervention."

“Doctors almost always describe DNA variants using various outdated or non-standard naming systems, or fail to accurately apply the current standard. This means they are publishing data which is less findable, so it may be missed by others in the field attempting to reach a diagnostic decision, denying the possibility of treatment,” added Dr. Freeman.

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