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.

中文翻译：

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实施单基因疾病的二元命名法


在确定基因在单基因疾病中的作用的证据强度时，一项核心任务是确定要管理的适当疾病实体。建立这个概念决定了哪些证据可以应用于和量化最终的基因疾病有效性、变异致病性或可操作性分类。对不止一种表型有影响的基因可能需要一个集中和分裂、疾病重组和疾病命名更新的过程。因此，重新评估用作疾病实体标签的名称是一个必要且永久的过程。临床基因组资源 （ClinGen） 与来自 Monarch 疾病本体论 （Mondo） 和人类在线遗传 （OMIM） 的代表合作，成立了疾病命名咨询委员会 （DNAC），为面临需要建立基因表型有效性和变异致病性的“精选疾病实体”的团体制定指南，并在必要时更新疾病名称以供临床使用。该小组的目标是与其他疾病相关专业小组合作，协调这些疾病学实体和 ClinGen 管理小组之间的疾病命名指南。在这里，我们介绍了 DNAC 制定的初步指南，以及 ClinGen 专家小组和工作组提供的代表性示例，这些示例需要更新命名法。我们还讨论了这些努力的更广泛影响及其对协调基因-疾病有效性管理的好处。总体而言，这项工作阐明了当前的不一致和/或差异，旨在让更广泛的社区了解 ClinGen 如何使用一致的疾病命名方法定义单基因疾病。