Implementation of a dyadic nomenclature for monogenic diseases.

A core task when establishing the strength of evidence for a gene's role in a monogenic disorder is determining the appropriate disease entity to curate. Establishing this concept determines which evidence can be applied and quantified toward the final gene-disease validity, variant pathogenicity, or actionability classification. Genes with implications in more than one phenotype can necessitate a process of lumping and splitting, disease reorganization, and updates to disease nomenclature. Reappraisal of the names that are used as labels for disease entities is therefore a necessary and perpetual process. The Clinical Genome Resource (ClinGen), in collaboration with representatives from Monarch Disease Ontology (Mondo) and Online Inheritance in Man (OMIM), formed the Disease Naming Advisory Committee (DNAC) to develop guidance for groups faced with the need to establish the "curated disease entity" for gene-phenotype validity and variant pathogenicity and to update disease names for clinical use when necessary. The objective of this group was to harmonize guidance for disease naming across these nosologic entities and among ClinGen curation groups in collaboration with other disease-related professional groups. Here, we present the initial guidance developed by the DNAC with representative examples provided by the ClinGen expert panels and working groups that warranted nomenclature updates. We also discuss the broader implications of these efforts and their benefits for harmonization of gene-disease validity curation. Overall, this work sheds light on current inconsistencies and/or discrepancies and is designed to engage the broader community on how ClinGen defines monogenic disorders using a consistent approach for disease naming.

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Déclaration de conflit d'intérêts

Declaration of interests M.H. is a co-founder of Alamya Health, a genomic diagnostics company. L.G.B. is a member of the Illumina Medical ethics committee and receives royalties from Wolters-Kluwer and research funding from Merck Inc.