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  1. FHIR Specification Feedback
  2. FHIR-19844

PGx High Risk Allele Medication Impact is confusing



    • Type: Change Request
    • Status: Triaged (View Workflow)
    • Priority: Medium
    • Resolution: Unresolved


      I think the term "risk allele" is generally used for disease-related variant assessment. As seen here (https://www.ashg.org/education/csertoolkit/commonrisk.html). I'm unclear as to why it would be used as a medication impact term. I think any sensitivity risk being high for a PGx variant-drug phenotype assertion would be more of the value or score of an assessed finding rather than the type of impact. For example, certain "alleles have a high risk of hypersensitivity to abacavir" or "DPYD*2A are at highest risk for severe or even fatal 5-fluorouracil" or event "individuals homozygous for TPMT*3A are at greatly increased risk for life-threatening myelosuppression when treated with standard doses of thiopurine drugs."
      Wouldn't these examples of high risk or increased risk be used as values on for the drug sensitivity or toxicity type assertion/interpretation?

      I am concerned because it seems like the ACMG may be considering adding the term "risk allele" to the list of 5 clinically significant disease classifications Path, Lik Path, VUS, Lik Ben and Benign to describe alleles that are not necessarily pathogenic but may be based on penetrance (or something like that). In any case, it strikes me as a confusing application of the terminology for this and reasons that misrepresent the impact that is being assessed (which I believe is "sensitivity").


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              Unassigned Unassigned
              lbabb Larry Babb
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