Several thousand rare genetic diseases have been described that together affect millions of people worldwide. Owing to advances in genomic sequencing, gene variants underlying such diseases have been identified and are collated and curated in databases, such as ClinVar and Leiden Open Variation Database (LOVD), with over 3 million unique variation records submitted to ClinVar and over 4.5 million entries in LOVD (as of 1 October 2024).

One of the key issues in correctly identifying gene variants and incorporating them into clinical use is the lack of standardized descriptions in available databases; for instance, they may be named by their genomic location, mRNA location without reference to the transcript in question, the nucleotide or amino acid change, or referred to by using older gene names. This not only hinders scientific progress, but can also result in misinterpretations, including false diagnosis or inappropriate disease management, thus directly affecting patient outcomes.

In their Comment in this issue, Freeman et al. present key updates to the open-source VariantValidator platform for standardized reporting of gene variants, which have been implemented since its original inception in 2018. Since then, the number of clinically relevant gene variants described in the literature has increased tremendously, necessitating improvements to the original platform.

Among the new functionalities are integration with Ensembl data, improved variant identification algorithms that can deal with imperfect alignments, and support for RNA descriptions, which are not typically provided by other validation tools.

These improvements were driven by engagement with the community through an agile development model, whereby users, including researchers, educators and clinicians, can test new releases, provide feedback and propose additional changes that would benefit their respective needs. This is an ongoing process, and developers continue to directly involve the community in the planning of new features and resources to ensure the platform can keep up with relevant advances in genomics.

Variant descriptions in VariantValidator fully adhere to the naming standards developed by the Human Genome Variation Society (HGVS). Moreover, the team behind the platform has joined a Human Genome Organization Reporting of Sequence Variants (HUGO RSV) committee, aimed at encouraging standard compliance in variant reporting by developing guidance for authors to use validation software prior to publication.

To facilitate the implementation of such standards, efforts are underway to establish a professional practice standard for the reporting and sharing of interpreted genomic variation. In collaboration with a working group led by the American College of Medical Genetics and Genomics (ACMG), the authors have developed a web-application programming interface, which generates a structured and standardized dataset that users can submit as supplementary material together with their manuscript.

In the long term, the goal is to integrate accurate validation and documentation of reported gene variants into the submission process. Until such an integration is realized, we encourage the genetics community to use VariantValidator prior to manuscript submission to work toward the goal of ensuring the accurate and standardized description of gene variants in both the literature and relevant databases used by the scientific community and clinicians.