The content in this section may be significantly revised prior to the next ballot after initial use and feedback.

The Genomic Implication profile is an abstract profile for Therapeutic and Diagnostic implications. Implications are relevant information which are derived from the presence of a haplotype, genotype, variant or other observed genetic change. This portion of the implementation guide relies on the content in the General Genomic Reporting and Variant Reporting portions of this implementation guide.

This profile defines a common set of elements for other Implications:

• Related Artifact (base extension) supports conveying references to citations, supporting documentation and other information relevant to the asserted implication
• evidence-level (component) indicates the strength of the evidence behind the asserted implication

Here are some examples of how the evidence-level component can be used (NOTE - they would be used in the appropriate, use case specific profile):

• Coded ACMG (see ACMG)
  

  {
    "valueCodeableConcept": {
      "coding": [{
        "system": "https://www.acmg.org",
        "code": "PS1",
      },
      {
        "system": "https://www.acmg.org",
        "code": "PM2"
      }
      ]
    }
  }
  			

• Coded PGx (see PharmGKB)
  

  {
    "valueCodeableConcept": {
      "coding": [{
        "system": "https://www.pharmgkb.org/",
        "code": "Level 1A",
      }
      ]
    }
  }
  			

• Coded Somatic (see MVLD)
  

  {
    "valueCodeableConcept": {
      "coding": [{
        "system": "https://www.clinicalgenome.org/mvld/",
        "code": "Tier1 LevelA",
      }
      ]
    }
  }
  			

Differentiating AND vs OR

There are several cases where it is necessary to differentiate 'AND' conditions (e.g. both drug X AND drug Y, in combination, are indicated in the presence of a variant) vs. 'OR' conditions (e.g., either drug X OR drug Y are indicated in the presence of a variant). This situation is not unique to genomic implications, and arises elsewhere within FHIR (e.g. FHIR Search) and outside of FHIR (e.g., ClinVar submission API condition set). To be consistent with other precedents:

Where Diagnostic and Therapeutic implications have fields with cardinality > 1, the inclusion of multiple values within a field SHALL indicate an 'AND' condition. An 'OR' condition SHALL be represented by multiple observation instances.

Implication fields affected by this guidance include:

Molecular consequences: derivedFrom, evidence-level, feature-consequence.

Therapeutic implications: derivedFrom, evidence-level, therapeutic-implication, phenotypic-treatment-context, medication-assessed, therapy-assessed.

Diagnostic implications: derivedFrom, evidence-level, predicted-phenotype, genomic-risk-assessment.

As an example, assume Variant X is pathogenic for Disease Y AND Disease Z in combination. This would be a single diagnostic implication, where predicted-phenotype is a list containing both Disease Y and Disease Z. If on the other hand, Variant X might be pathogenic for Disease Y alone, or Disease Z alone, this would be two diagnostic implications, one containing a predicted-phenotype of Disease Y, and the other containing a predicted-phenotype of Disease Z.