@echeetham
Ed,
Thanks for your detailed and thorough analsis of the revised proposal. I am happy to see we are going in the right direction. Your comments have been very helpful in identifying areas of the proposal that require additional clarification and detail. I hope the responses below address the concerns you listed and there will be changes to the document to ensure that your concerns are addressed.
1. Scope and intended utility
This proposal defines a structural representation for clinically relevant human gene names within SNOMED CT, solely to support the authoring, definition, and classification of SNOMED CT content such as Clinical findings, Disorders, and Observable entities. It is not intended to provide a comprehensive gene catalogue, to support primary recording or reporting of molecular test results, or to replace external gene nomenclature or reporting standards (e.g. HGNC), although it seeks to align with external genomic standards. The wording “Provide a structured list of clinically relevant gene names associated with their respective chromosomes that can be used as values in molecular testing” was misleading. It was intended to describe the use of gene names in the modeling and definition of gene-specific content in SNOMED CT, such as Observable entities, Clinical findings, and Disorders, and not to imply support for the direct recording or reporting of gene names as molecular test results. This will be corrected in the next version of the document. I hope this clarifies the scope.
2. Finding site vs. Associated gene
We acknowledge that the proposal does not clearly distinguish between the use of Finding site and the new “Associated gene” attribute, which results in ambiguity in the examples. Finding site is intended for use only when the specific chromosomal structure (i.e. arm or band) or gene itself is the locus of the abnormality (e.g. a mutation or deletion affecting the chromosome or gene structure). In other cases where a gene is referenced to indicate etiological involvement rather than the anatomical site of change, the gene should be modeled using the “associated gene” attribute. The proposal will be updated to make the editorial guidance regarding use of gene names explicit to ensure consistent modeling.
Regarding the name of the recommended new attribute, the existing name in the proposal is for example only. We are reviewing attribute names in other terminologies to assist in semantically correct name assignment for this attribute, along with the text definition. The new proposed name will conform (as you suggest) to the verb form as well being explicit as to the nature of the relationship of the gene to the associated disorder. This will be included in the next version of the proposal.
3. Chromosome banding
3.1 Why not add all bands?
The proposal does not assert that unused chromosome band concepts are inappropriate. The initial implementation prioritizes those bands required to support existing international content and known use cases, with the expectation that additional bands may be added incrementally over time. This approach is consistent with how SNOMED CT has historically managed growth within the Anatomy and Morphology hierarchies. The International System for Human Cytogenomic Nomenclature (ISCN 2024) defines between approximately 400 major bands and 850 major and sub-bands. Not all of these are necessary to locate clinically relevant genes or to support karyotype-related findings within the scope of this proposal. Limiting the initial addition of chromosome band concepts to those required for defined use cases is a pragmatic editorial approach. If large-scale addition of bands is identified as a use case, SNOMED will investigate sources that can facilitate bulk inclusion of this content.
3.2 Band spans (e.g. 9q33.3–9q34.11)
SNOMED CT does not generally introduce explicit concepts for anatomical or structural ranges, particularly where the potential set of ranges is open-ended. In light of this, disorders named using chromosomal band ranges (e.g. 1228886008 |9q33.3-9q34.11 microdeletion syndrome (disorder)|) do not require the introduction of explicit “band range” structure concepts. These disorders can remain primitive and be modeled using the appropriate chromosome arm (e.g. long arm of chromosome 9), which correctly represents the structural locus at the level of granularity supported by the terminology. This approach is consistent with existing SNOMED CT editorial practice and avoids the need to introduce a potentially unbounded set of range concepts.
3.3 Risk of false subsumption: gene abnormality <> band abnormality
We agree that inappropriate subsumption between gene abnormality disorders and karyotype abnormality disorders must be avoided. This is addressed by modeling gene abnormalities using gene structures as the locus of change, while karyotype abnormalities reference chromosome- or band-level structures, typically in combination with the affected chromosome pair. This approach maintains a clear separation of concerns between gene-level and chromosome-level abnormalities, preserving the intended inference direction and aligning with existing SNOMED CT modeling practice. This, of course, will be part of the review of the modeling impact.
3.4 Chromosome pairs vs. bands vs. current classification
The Appendix 1 example for Microdeletion of chromosome 15q24 (disorder) inadvertently omits the chromosome pair role group that is present in current international modeling of karyotype abnormalities. This will be corrected in the next version of the document to align the example with existing SNOMED CT content patterns. The omission does not reflect a change in modeling approach, nor does it imply that chromosome pair involvement would be lost under the proposed structure.
4. Process - Changes already enacted
Updates to chromosomal anatomy, including the addition of specific chromosome structures and chromosome arms, have already been implemented to address longstanding gaps in the body structure hierarchy. These changes were independently justified to improve modeling of existing content and are not contingent on the outcome of this proposal. They also establish a structural foundation for the potential addition of chromosome bands and gene names, which remain subject to consultation. The document will be updated to reflect the completion of the affected elements of the proposal.
5. Impact beyond terminology development, i.e. testing
This proposal is necessarily focused on the authoring and modeling of gene and chromosomal content, as establishing a coherent and semantically sound structure is a prerequisite for evaluating downstream use. Consideration of classification behavior, data entry, analytics, and interoperability occurs once proposed content has been modeled and tested, and forms part of established SNOMED CT quality assurance and release processes. This evaluation will also involve any existing Clinical finding, Disorder, or Observable entity concepts that are remodeled to use the new gene and chromosome band structures. It is also recognized that the absence of gene concepts in SNOMED CT has already limited the quality and precision of modeling in these areas, which itself represents a downstream impact. Following this review, any identified issues will be addressed prior to content promotion to the International release.