Standardization of Genomic Nomenclature across a Diverse Ecosystem of Stakeholders: Evolution and Challenges

Genetic testing has traditionally been divided into molecular genetics and cytogenetics, originally driven by the use of different assays and their associated limitations. Cytogenetic technologies such as karyotyping, fluorescent in situ hybridization or chromosomal microarrays are used to detect large "megabase level" copy number variants and other structural variants such as inversions or translocations. In contrast, molecular methodologies are heavily biased toward subgenic "small variants" such as single nucleotide variants, insertions/deletions, and targeted detection of intragenic, exon level deletions or duplications. The boundaries between these approaches are now increasingly blurred as next-generation sequencing technologies and their use for genome-wide analysis are used by both disciplines, therefore eliminating the historic and somewhat artificial separation driven by variant type.

This review discusses the history of genomic nomenclature across both fields, summarizes implementation challenges for the clinical genetics community, and identifies key considerations for enabling a seamless connection of the stakeholders that consume variant descriptions.

Standardization is naturally a lengthy and complex process that requires consensus building between different stakeholders. Developing a standard that not only fits the multitude of needs across the entities that consume genetic variant information but also works equally well for all genetic variant types is an ambitious goal that calls for revisiting this vision.