Interpretation

This message intends to represent the interpretation of a genomic analysis, such as the report from a diagnostic laboratory.

Data model

Field Type Multiplicity Description
id string 1..1 Arbitrary identifier. REQUIRED.
progress_status ProgressStatus 1..1 The current resolution status. REQUIRED.
diagnosis Diagnosis 0..* One or more diagnoses, if made
summary string 0..1 Additional data about this interpretation

Example

In this example, a case with id CONSORTIUM:0000123456 is reported to be solved. The diagnosis is Miller syndrome, and the supporting interpretation states the involved gene. For privacy reasons, the variant was not reported, but the intended meaning is that a relevant variant in the named gene was found.

interpretation:
  id: "CONSORTIUM:0000123456"
  progressStatus: "SOLVED"
  diagnosis:
    disease:
      id: "OMIM:263750"
      label: "Miller syndrome"
    genomicInterpretations:
    - interpretationStatus: "CONTRIBUTORY"
      gene:
        valueId: "HGNC:2867"
        symbol: "DHODH"

Explanations

id

The id has the same interpretation as the id element in the Individual element.

ProgressStatus

The interpretation has a ProgressStatus that refers to the status of the attempted diagnosis.

Implementation note - this is an enumerated type, therefore the values represented below are the only legal values. The value of this type SHALL NOT be null, instead it SHALL use the 0 (zero) ordinal element as the default value, should none be specified.

Name Ordinal Description
UNKNOWN_PROGRESS 0 No information is available about the diagnosis
IN_PROGRESS 1 No diagnosis has been found to date but additional differential diagnostic work is in progress.
COMPLETED 2 The work on the interpretation is complete.
SOLVED 3 The interpretation is complete and also considered to be a definitive diagnosis
UNSOLVED 4 The interpretation is complete but no definitive diagnosis was found

Diagnosis

The diagnosis element is meant to refer to the disease that is inferred to be present in the individual or family being analyzed. The diagnosis can be made by means of an analysis of the phenotypic or the genomic findings or both. The element is optional because if the resolution_status is UNSOLVED then there is no diagnosis.

Data elements

Field Type Multiplicity Description
disease OntologyClass 1..1 The diagnosed condition. REQUIRED.
genomic_interpretations GenomicInterpretation 0..* The genomic elements assessed as being responsible for the disease or empty

Examples of the intended usage of the Interpretation element

Candidate genes

Research consortia may exchange information about candidate genes in which an undisclosed variant was found that was assessed to be possibly related to a disease or phenotype but for which insufficient evidence is available to be certain. The intention is often to find other researchers with similar cases in order to subsequently share detailed information in a collaborative project.

In this case, the gene should be marked as CANDIDATE. Here is an example of an interpretation with the hypothetical gene YFG42.

interpretation:
  id: "CONSORTIUM:0000123456"
  progressStatus: "SOLVED"
  diagnosis:
    disease:
      id: "OMIM:263750"
      label: "Miller syndrome"
    genomicInterpretations:
    - interpretationStatus: "CONTRIBUTORY"
      gene:
        valueId: "HGNC:2867"
        symbol: "DHODH"

Diagnostic finding in an autosomal dominant disease

The Interpretation element might be used in this way to report a laboratory finding in a diagnostic setting or in a published case report. The following example shows how the variant NM_000138.4(FBN1):c.6751T>A (p.Cys2251Ser) would be reported.

interpretation:
  id: "Arbitrary interpretation id"
  progressStatus: "SOLVED"
  diagnosis:
    disease:
      id: "OMIM:154700"
      label: "Marfan syndrome"
    genomicInterpretations:
    - subjectOrBiosampleId: "subject 1"
      interpretationStatus: "CONTRIBUTORY"
      variantInterpretation:
        acmgPathogenicityClassification: "PATHOGENIC"
        variationDescriptor:
          expressions:
          - syntax: "hgvs"
            value: "NM_000138.4(FBN1):c.6751T>A"
          allelicState:
            id: "GENO:0000135"
            label: "heterozygous"

The subjectOrBiosampleId is set to the id of the Individual of the enclosing phenopacket to indicate that the genomic interpretation refers to a germline variant.

Diagnostic finding in an autosomal recessive disease

For homozygous variants, the zygosity would be set to homozygous. The following example shows a finding of compound heterozygous variants.

interpretation:
  id: "Arbitrary interpretation id"
  progressStatus: "SOLVED"
  diagnosis:
    disease:
      id: "OMIM: 219700"
      label: "Cystic fibrosis"
    genomicInterpretations:
    - subjectOrBiosampleId: "subject 1"
      interpretationStatus: "CONTRIBUTORY"
      variantInterpretation:
        acmgPathogenicityClassification: "PATHOGENIC"
        variationDescriptor:
          expressions:
          - syntax: "hgvs"
            value: "NM_000492.3(CFTR):c.1477C>T (p.Gln493Ter)"
          allelicState:
            id: "GENO:0000135"
            label: "heterozygous"
    - subjectOrBiosampleId: "subject 1"
      interpretationStatus: "CONTRIBUTORY"
      variantInterpretation:
        acmgPathogenicityClassification: "PATHOGENIC"
        variationDescriptor:
          expressions:
          - syntax: "hgvs"
            value: "NM_000492.3(CFTR):c.1521_1523delCTT (p.Phe508delPhe)"
          allelicState:
            id: "GENO:0000135"
            label: "heterozygous"

The subjectOrBiosampleId is set to the id of the Individual of the enclosing phenopacket to indicate that the genomic interpretation refers to a germline variant.

Diagnostic finding in a cancer

Cancer cases are not generally solved by genomic analysis. Instead, the intention is often to identify actionable variants that represent potential indications for targeted therapy. In this example, a BRAF variant is interpreted as being actionable in this sense.

interpretation:
 id: "Arbitrary interpretation id"
 progressStatus: "COMPLETED"
 diagnosis:
   disease:
     id: "NCIT:C3224"
     label: "Melanoma"
   genomicInterpretations:
   - subjectOrBiosampleId: "biosample id"
     interpretationStatus: "CONTRIBUTORY"
     variantInterpretation:
       acmgPathogenicityClassification: "PATHOGENIC"
       therapeuticActionability: "ACTIONABLE"
       variationDescriptor:
         expressions:
         - syntax: "hgvs"
           value: "NM_001374258.1(BRAF):c.1919T>A (p.Val640Glu)"
         allelicState:
           id: "GENO:0000135"
           label: "heterozygous"

The subjectOrBiosampleId is set to the id of the Biosample that is contained in the enclosing phenopacket, representing a biopsy from a melanoma sample taken from the subject of the phenopacket.