Accurate documentation of variation in our genomes is important for research and clinical care and it is essential that this documentation be standardized. To address this issue, the Human Variome Project convened a committee in 2018 to evaluate the feasibility of requiring authors to verify that all variants submitted for publication comply with a widely accepted standard for their description. Members of the Variants in Journals (VIJ) committee represented expertise in journal publication, variant description and data sharing. Following a series of monthly committee discussions and consultations with external experts over a two-year period, a consensus was reached that all published variants should conform to criteria developed by the Human Genome Variation Society (HGVS), the HGVS nomenclature standard. Committee members agreed that authors are responsible for the accuracy of variant description and should, as a minimum, be required to confirm in writing that all variants reported in their manuscripts conform to HGVS nomenclature. In addition, the committee recommended that editors should request evidence of verification in the form of output files from online publicly available software tools, or records documenting submission to online databases that verify nomenclature [e.g., ClinVar, Leiden Open Variaton Database – LOVD] Provision of such evidence would assist authors and editors should database curators or others question variant descriptions or identify variants that cannot be described according to HGVS nomenclature.

To assess the burden that these requirements might place on authors and editors, staff at two journals (Human Mutation and Genetics in Medicine) performed a pilot project. Compliance with description requirements and recurrent issues were documented over a period of 4 months. Concurrently, staff who developed and implemented validation tools (Mutalyzer and VariantValidator) agreed to provide assistance to authors and to document unresolved issues. These concepts were explained in a Commentary authored by the committee entitled: Verifying nomenclature of DNA variants in submitted manuscripts: Guidance for journals, published in 2021 (https://doi.org/10.1002/humu.24144).

Several issues surfaced during the pilot project. Prime among these was the question of whether journal editors or authors should be responsible for correcting nomenclature errors. Two factors contributed to the committee’s response to this issue: 1) authors have primary responsibility for the accuracy of all data presented in their publications, and 2) editorial staff do not have sufficient expertise or work-force capacity to perform accuracy checks. Therefore, the committee decided that authors should have final responsibility for correcting the nomenclature of any variants not conforming to HGVS nomenclature. In addition, because a substantial fraction of published variants have documented nomenclature errors, the committee decided that all variants presented in a manuscript, whether new or previously reported, should be verified. This approach will progressively correct extant nomenclature errors. Mutalyzer and VariantValidator autocorrect variant descriptions and create warnings in their results file, except on rare occasions where there are syntax errors that cannot be interpreted/resolved or HGVS expressions are used that these tools do not support. LOVD developed a tool that aims to recognize and correct common syntax errors as well as support HGVS expressions that cannot be validated by the aforementioned tools. The HGVS nomenclature committee can assist when autocorrection does not occur (through the documentation or the Google discussion group).

In 2021, the VIJ committee came under the auspices of the Human Genome Organization (HUGO) when HGVS and the Human Variome Project joined HUGO. Concurrently, the Committee was reformulated as the HUGO Reporting of Sequence Variants Working Group. In an effort to achieve adoption of the guidelines, the Working Group approached manuscript processing system vendors, and ultimately engaged Aries (https://www.ariessys.com/), who have integrated variant validation into their Editorial Manager submission system, making the validation of DNA variants easy for authors. Adoption of the validation software by other submission systems would lead to widespread application across many publishers and journal types. Other journals and publishers will be contacted in the future to encourage adoption of methods to ensure accurate standardized reporting of variants in their publications.

Current Members

Garry Cutting, Johns Hopkins University,
Prior Hum. Mut. Editor

Peter Freeman, University of Manchester,
GiM and GiMO. Senior technical editor and Patient editor. VariantValidator PI

David N. Cooper, Cardiff University,
Co-Editor, Human Genetics

Raymond Dalgelish, University of Leicester,
HVP, VariantValidator PI

Johan den Dunnen, Leiden University,
LOVD/HVP/Human Mutation

Huw Dorkins, University of Oxford,
Editor in Chief, Journal of Medical Genetics

Diane Drexler, ACMG,
Managing Editor, Genetic in Medicine

Michael Fletcher, Nature Genetics,
Sr. Editor, Nature Genetics at Spring Nature

Ivo Fokkema, Leiden University Medical Center,
PI of the Leiden Open Variation Database LOVD project

Li Gong, Stanford University,
Sr. Curator, PharmGKB

Issei Imoto, Aichi Cancer Center Research Institute,
Human Genome Variation/EIC

Terri Klein, Stanford University,
PharmGKB

Bruce Korf, University of Alabama,
Editor in Chief, AJHG

Adya Misra, SAGE Publishing,
Sr. Editor, PLos ONE/Peerj

Heidi Rehm, Harvard University,
Clin Gen/GA4GH, Editor Cold Harbor

Jurgen Reichardt, James Cook University,
HuGO Exec. Board; Exec. Ass. Editor Human Genomics

Prior Members

Greg Barsh, PLoS Genetics

Sara Cullinan, American Journal of Medical Genetics

Kay Davies, Human Molecular Genetics

James Evans, Genetics in Medicine

Jan Higgins, Genetics in Medicine/ACMG

Constantin Polychronakos, Journal of Medical Genetics

Sarah Ratzel, American Journal of Medical Genetics

Katsushi Tokunaga, Human Genome Variation

Karen Weck, Genetics in Medicine