Scope

Genomics is a rapidly evolving area of healthcare that involves complex data structures. There is significant value in sharing this information in a way that is consistent, computable and that can accommodate ongoing evolution of medical science and practice. At present, this implementation guide focuses solely on data structures - what data should be/might be present and how it should be organized. It does not address workflows around how reports are requested, created, approved, routed, delivered, amended, etc.

This guide covers many aspects of genomic data reporting, including:

• Representation of simple discrete variants, structural variants including copy number variants, complex variants as well as gross variations such as extra or missing chromosomes
• Representation of both known variants as well as fully describing de novo variations
• Germline and somatic variations
• Relevance of identified variations from the perspective of disease pathology, pharmacogenomics, transplant suitability (e.g., HLA typing), etc.
• Full and partial DNA sequencing, including whole genome and exome studies

How to Use this Guide

This implementation guide is organized into a set of sections. All implementers intending to do clinical genomic reporting should read the General Genomic Reporting and the Variant Reporting sections. To understand the key profiles in this IG, as well as their relationship to one another, start with the General Genomics Reporting section. Those new to FHIR should review the Understanding FHIR section below.

The remaining sections provide support for more specialized types of reporting. If your system is involved with genomic reports in a particular area, then read through that section of the implementation guide for further guidance.

Background	Introduces some of the key genomics terms and relationships that should be understood by those implementing this specification.
General Genomic Reporting	Overall guidance in using the profiles and transactions defined in this guide. Guidance and examples for the general structure of genomic reports, how to report overall interpretations and how to report genotypes, haplotypes, and different types of variants.
Variant Reporting	Guidance on expressing information about variants gleaned from various sequencing approaches including direct sequencing, shotgun sequencing, array-based testing, etc.
Pharmacogenomic Reporting	Guidance and examples related to genomic testing done for the purpose of assessing genomic variations' implication on the use of medications - both for oncology and for general patient treatment.
Somatic Reporting	Guidance related to genomic testing done on somatic (non-germline) tissues, including assessments of tumors.
Histocompatibility Reporting	Guidance related to genomic testing done for histocompatibility and immunogenomics assessments, including HLA typing.

Guiding principles

This guide adheres to a set of design approaches:

• It is intended to be international in scope and only leverages terminologies which are freely available to all countries.
• It avoids pre-coordinating the type of variant, medication, or other information into the Observation.code as this makes it easier to leverage industry standard terminologies for genomic information (e.g., HGVS) and avoids needing to duplicate this information into observation coding systems such as LOINC.
• It maximizes the use of resources that are in common use by laboratory reporting systems for other clinical areas - specifically Observation and DiagnosticReport. This eases implementation and also reduces the chance of data being lost by systems that might not have been designed to specifically accommodate genomic-related information.
• It minimizes the use of FHIR extensions, also with an objective of reducing the risk of data loss when information is passed to systems that might not explicitly support this implementation guide.
• It uses separate observations for each independently useful assertion. This makes the data discoverable and queryable as seen in the query guidance. Also review the guidance on the proper usage of contained resources.
• It tries to ensure that data is captured in a manner that's consistent regardless of the type of testing that was done to ensure data can be consistently queried even if captured differently (e.g., variations identified in assay tests are reported in the same manner as those identified through direct sequencing).
• The guide allows for variability in the amount of discrete information captured. Systems are encouraged to populate what discrete elements they can and allows for the possibility of systems populating additional elements as their technical capability and/or time and other resources allow.

Together, these principles should make adoption easier and allow systems to more easily adapt in a compatible way as genomic reporting continues to evolve.

Previous Specifications

FHIR STU3 included a set of profiles that provided guidance on how to convey genomic orders, results, and observations. Those profiles are superseded by this implementation guide. Guidance for converting from these older profiles is found here.

Understanding FHIR

This implementation guide is based on the HL7 FHIR standard. It uses terminology, notations and design principles that are specific to FHIR. Before reading this implementation guide, it's important to be familiar with some of the basic principles of FHIR as well as general guidance on how to read FHIR specifications. Readers who are unfamiliar with FHIR are encouraged to read (or at least skim) the following prior to reading the rest of this implementation guide.

• FHIR overview
• Developer's introduction
• (or Clinical introduction)
• FHIR data types
• Using codes
• References between resources
• How to read resource & profile definitions
• Base resource
• FHIR Validation

It is highly recommended that readers review Diagnostics Module and review the resources that are used as part of this implementation guide, especially Observation, DiagnosticReport, and MolecularSequence.

Importantly, implementers should pay close attention to the considerations in Associated Observations and Observation Grouping describing proper usage of the relationships DiagnosticReport.result, Observation.hasMember>, and Observation.derivedFrom. Consumers of Genomic diagnostic reports MUST navigate through all hasMember relations, and navigate through derivedFrom relationships in order to ensure all clinically relevant information is seen.

Many Observation profiles and components in this guide require sending codes from http://loinc.org. If necessary for implementation (e.g., to map to a local system), equivalent codes from other code systems may *also* be sent, following the guidance on observation.

Since this Implementation Guide is not targeting a specific country or region, other requirements may be needed for local reporting. Observation instances adhering to other profiles should be built to validate against one of this Implementation Guide’s profiles wherever possible. Where incompatibilities may arise, it is most important to align with the codes and values for Observations and their components.

Extending beyond this Guide

Implementers should use this guide to structure genomics data in an interoperable way. The Clinical Genomics Working Group understands that this guide is not complete, and implementers might identify additional concepts and data elements. Please review this guidance for ways to handle those use cases.

Appendices

Appendix A: Relation to v2 reporting	Links to v2 Genetic Variation Model Implementation Guide and v2 Cytogenomic Model Implementation Guide
Appendix B: Clinical Genomics Apps	Introduction of the Clinical Genomics Applications (Genomics Advisor, etc) apply for this implementation guide
Appendix C: Domain Analysis Model	A domain analysis model for various use cases in clinical genomics
Appendix D: Query Guidance	Query guidance based on use-cases from the Domain Analysis Document
Appendix E: External Coding Systems	Reference for publicly available external coding systems
Appendix F: Conversion from STU3 Extensions	Note on deprecated extensions defined in FHIR STU3
Appendix G: Molecular Sequence	Notes on the FHIR Resource for representing a Molecular Sequence
Appendix H: Grouping observations	Guidance on the types of grouping that might be encountered
Appendix I: Glossary	Table of concepts referenced on Observation profiles

Acknowledgments

The Clinical Genomics Reporting Implementation Guide is a product of the HL7 Clinical Genomics Work Group. Questions or comments regarding this implementation guide should be directed to the HL7 Clinical Genomics Work Group at clingenomics@lists.hl7.org.

The authors of this guide wish to recognize the following participants who contributed their time and expertise to the continued development of this guide:

Name	Organization	Role
Bob Milius	NMDP/CIBMTR	CG Co-Chair
Mullai Murugan	Baylor College of Medicine	CG Co-Chair
Patrick Werner	MOLIT Institut	CG Co-Chair
Kevin Power	Cerner	CG Co-Chair
Jamie Jones	Boston Children's Hospital	CG Co-Chair
Bob Freimuth	Mayo Clinic	CG Co-Chair, IM Sub-Group Lead
Arthur Hermann	Kaiser Permanente	Contributor
Kevin Roberg-Perez	Bioi	Contributor
Anand Kulanthaivel	Clinical Architecture	Contributor
JD Nolen	Children's Mercy Hospital	Contributor
Joel Schneider	NMDP/CIBMTR	Contributor
Liz Amos	National Library of Medicine	Contributor
Bob Dolin	Elimu Informatics	Contributor
May Terry	MITRE	Contributor
Bret Heale	Intermountain	Contributor
Rachel Kutner	Epic	Contributor
Clem McDonald	National Library of Medicine	Contributor
Ling teng	BWH	Contributor
Dora Walter	MOLIT Institut	Contributor
Lloyd McKenzie	Gevity	Contributor
Alex Mankovich	Philips	Contributor
Daniel Rutz	Epic	Contributor
Larry Babb	Broad	Contributor
Peter Muir		Contributor
Aly Khalifa	Mayo Clinic	Contributor