Interpretation Model

Introduction

ClinGen members are generating an incredible amount of richly curated interpretations of the clinical effect of genetic variants. The ClinGen Interpretation Model provides a structure and format for exchanging this information, which retains the contextual and supporting information related to the interpretation of the variant.

Benefits of the ClinGen Interpretation Model

  • Captures a rich set of data around an interpretation:
    • What evidence was used in this interpretation
    • How the evidence supported or conflicted with the interpretation
    • Who performed each individual act in the creation of an interpretation
    • The sources of the data used in the interpretation
    • How the explicitly defined criteria were applied to the evidence
    • To what degree the interpretation builds upon previous interpretations
  • Aligns with related community models including:
  • Other features:
    • Flexibility: This model is naturally able to represent a range of interpretation depth, from unsupported assertions to fully evidence-based interpretations, using whatever level of data has been captured.
    • Contains an extensive set of data objects for representing frequently used information
    • Defines a message structure using industry-standard JSON
    • Extensible: Easily transferable to other types of interpretations other interpretation methods
    • Well-documented, including many examples of using the model to encode variant interpretations using all of the ACMG guidelines

Development by Example

To ensure that the model supports its intended use case to represent clinical interpretation of variants, development has been guided by real-world examples based on the application of the ACMG guidelines. These examples are available in hierarchical form through the individual pages of the Technical Reference, or in a "flattened" form in the data/flattened directory of our source code repository.

Status

Version 1 of the interpretation model was released October 13, 2017, and allows the description of variant pathogenicity interpretations based on the ACMG guidelines. Version 2 will incorporate variant interpretations across a broader set of entities and styles, and is currently in the scoping phase.

Documentation

The documentation for the Interpretation Model is divided into two sections. The User Guide is meant for those new to the model, and for those seeking a non-technical explanation describes the structure of the model and its relationships to Monarch SEPIO and W3C-Prov. The Technical Reference is for technical users and implementers of the model who are already familiar with the overall structure of the model. The Technical Reference includes detailed information about the data types and attributes used in the data model, as well as numerous examples that show how these types are expressed in a JSON format.