Existing Wording: At present, impacts are noted as explicit observations about the patient/subject. However, it's not clear this is the correct approach. The work group is evaluating introducing a new resource that allows conveying "knowledge" about a variant in a patient-independent way. This would allow saying "this variant is associated with an increase risk of cardiovascular disease" rather than "based on this variant, the patient is at an increased risk of cardiovascular disease", which isn't necessarily a determination the reporting organization may wish to assert. Feedback is welcome.

Comment:

This is an area we?ve discussed in the course of developing the CG v3 specs. Consider for example the information included in a paper curated in the following OMIM Entry:

?Despite the dramatic responses to EGFR inhibitors in patients with non-small cell lung cancer, most patients ultimately have a relapse.

reported a patient with EGFR-mutant, Gefitinib-responsive, advanced non-small cell lung cancer who had a relapse after 2 years of complete remission during treatment with Gefitinib. The DNA sequence of the EGFR gene in his tumor biopsy specimen at relapse revealed the presence of a second mutation (

). Structural modeling and biochemical studies showed that this second mutation led to the Gefitinib resistance.?

At the time when the ?second mutation? was revealed, there?s a basis to assert that the first mutation led to the situation of the patient being Gefitinib-responsive. At this point in time, what should be the nature of the association of the first versus the second mutation to the responsiveness to Gefitinib? I would argue the first association is sort of retrospective and can be asserted with more certainty to that specific patient, while the second association could be seen as linking to knowledge.

These issues should be discussed in a broader sense, that is, broader than genetic testing scenarios, rather - the future state of a longitudinal health record of the patient where we expect the ?dots to be connected? as much as possible, surfacing up insights from a broader perspective along the various dimensions of time, content and types of data.

Summary:

knowledge representation