MII IG Kerndatensatz-Modul Molekulargenetischer Befundbericht
2027.0.0-ballot.1 - Germany

This page is part of the MII IG Kerndatensatz-Modul Molekulargenetischer Befundbericht (v2027.0.0-ballot.1: Release) based on FHIR (HL7® FHIR® Standard) R4. This is the current published version. For a full list of available versions, see the Directory of published versions

Profiles

This page lists the FHIR profiles of the Molekulargenetischer Befundbericht module (naming convention MII_PR_<Module>_<Name>, see the docs/recipes/add-a-profile.md in this repository, and the MII naming conventions). The module's extensions are listed on the Extensions page.

Profile inheritance hierarchy

FHIR profiles

Guidance on using the elements when reporting variants can be found in the Genomics Report profile from the HL7 Genomics Reporting Implementation Guide.

The following table shows the inheritance relationships of the profiles in this module:

Profiles based on Clinical Genomics STU3
Profile name Parent profile (STU3) Description
MII_PR_MolGen_MolekulargenetischerBefundbericht genomic-report Main report for genetic analyses
MII_PR_MolGen_Variante variant Genetic variant
MII_PR_MolGen_Genotyp genotype Genotype information
MII_PR_MolGen_DiagnostischeImplikation diagnostic-implication Diagnostic significance
MII_PR_MolGen_TherapeutischeImplikation therapeutic-implication Therapeutic significance
MII_PR_MolGen_MolekulareKonsequenz molecular-consequence Molecular effect
MII_PR_MolGen_Medikationsempfehlung medication-recommendation Medication recommendation
MII_PR_MolGen_EmpfohleneFolgemassnahme followup-recommendation Recommended follow-up action
MII_PR_MolGen_GenomicStudy genomic-study Genomic study
MII_PR_MolGen_GenomicStudyAnalysis genomic-study-analysis Analysis within the genomic study
MII_PR_MolGen_MolekularerBiomarker molecular-biomarker Base profile for the biomarker profiles of this module
Profiles derived from another profile of this module
Profile name Parent profile Description
MII_PR_MolGen_Mikrosatelliteninstabilitaet MII_PR_MolGen_MolekularerBiomarker MSI status
MII_PR_MolGen_Mutationslast MII_PR_MolGen_MolekularerBiomarker Tumor mutational burden

Both reach Clinical Genomics STU3 through MII_PR_MolGen_MolekularerBiomarker, not directly.

Two canonical URL schemes — deliberate, not an oversight

Twelve profiles carry a short canonical, four carry one prefixed with mii-pr-molgen-:

Scheme Canonical ends in Profiles
short …/StructureDefinition/variante the twelve older profiles
prefixed …/StructureDefinition/mii-pr-molgen-genomic-study GenomicStudy, GenomicStudyAnalysis, MolekulareKonsequenz, MolekularerBiomarker

The four prefixed ones were added during the migration to Clinical Genomics STU3 and picked up the prefix from their ids. The two GenomicStudy profiles also kept their English names, where the rest of the module names profiles in German.

This is not going to be harmonised. All four canonicals shipped in version 2026.0.4, so they are established identity: anyone using that release has these URLs in profile bindings, in meta.profile and in search queries. Renaming them would break those references, and a ballot is the wrong moment — reviewers would be checking content and fighting broken references at the same time. Whether a common convention should apply across all MII core dataset modules is a question for the TF-KDS, not for this module alone.

When writing a reference by hand, take the canonical from the profile's own page rather than deriving it from the profile name.

Profiles derived directly from FHIR R4
Profile name Parent resource (FHIR R4) Description
MII_PR_MolGen_AnforderungGenetischerTest ServiceRequest Request for genetic testing
MII_PR_MolGen_Familienanamnese FamilyMemberHistory Family history
MII_PR_MolGen_PolygenerRisikoScore RiskAssessment Polygenic risk score

Profile relationship diagram

The following diagram visualizes the relationships between the various FHIR profiles in the module:

MII Kerndatensatz Modul Molekulargenetik - Profil-Beziehungen

Legend:

  • Blue (workflow): ServiceRequest and DiagnosticReport as the central workflow components
  • Turquoise (study): GenomicStudy and GenomicStudyAnalysis for study data
  • Green (finding): Genetic findings (variant, genotype, haplotype)
  • Orange (biomarker): Molecular biomarkers (MSI, mutational burden, PRS)
  • Purple (implication): Clinical implications (diagnostic, therapeutic, molecular)
  • Grey (task): Recommended actions (medication, follow-up)

Workflow: request and report

Overview: workflow

The workflow for molecular genetic analyses covers the entire process, from requesting a genetic examination through to producing the final report.

Core components of the workflow

ServiceRequest (request): initiates the diagnostic process with specific questions and the desired analyses.

DiagnosticReport (report): the central resource that brings together all results, interpretations and recommendations and presents them in a structured form.

Workflow sequence

  1. Request: the clinician requests genetic testing together with the clinical question
  2. Sample collection: obtaining and preparing the sample (referenced through Specimen)
  3. Performance: genetic analysis by means of GenomicStudy
  4. Evaluation: identification of variants and their interpretation
  5. Report creation: consolidation of all results in the DiagnosticReport
  6. Recommendations: derivation of therapeutic or diagnostic consequences
  • ServiceRequest → DiagnosticReport via basedOn
  • DiagnosticReport → GenomicStudy via extension
  • DiagnosticReport → Observations via result
  • DiagnosticReport → Tasks via the recommended-action extension

Genetic findings

Overview: genetic findings

Genetic findings document the identified genetic variants and their molecular properties. These Observation-based profiles form the factual basis for molecular genetic diagnostics, without interpretive assessments.

Core profiles: genetic findings

Variant: a single genetic change with detailed molecular annotations.

Genotype: combination of alleles at a particular gene locus, important for inheritance analysis.

Haplotype: group of linked genetic variants that are inherited together.

Sequence Phase Relationship: describes the phase relationship between variants (cis/trans).

Important components of the variant

Molecular annotation
  • HGVS notation at different levels (genomic, transcript, protein)
  • Reference sequences (MANE transcripts preferred)
  • Genomic position (chromosome, start, end)
  • Reference and alternate alleles
  • Gene symbol (HGNC)
Allelic state
  • Zygosity (heterozygous, homozygous, hemizygous)
  • Allele frequency (VAF - variant allele frequency) in the examined sample
  • Allelic read depth (number of reads per allele)
  • Variants can be grouped into genotypes (hasMember)
  • Genotypes can form haplotypes
  • All findings reference the associated GenomicStudy via partOf
  • Interpretations in the implications point to these findings via derivedFrom

Scope of the genetic findings

Not contained in the findings:

  • Pathogenicity and clinical significance → see the implications
  • Coverage and sequencing depth → see the methodology (GenomicStudy)
  • Quality metrics → see the methodology (GenomicStudyAnalysis)

Genetic implications

Overview: genetic implications

Genetic implications assess and interpret the identified genetic findings with respect to their clinical significance. These Observation profiles contain the medical classification of the variants.

Core profiles: genetic implications

Diagnostic implication: assesses the significance of a variant for making the diagnosis and for the cause of the disease.

Therapeutic implication: describes the effects on therapy decisions and the choice of medication.

Molecular consequence: documents the functional effects on gene products (proteins, RNA).

Important components: genetic implications

Clinical assessment
  • Pathogenicity according to the ACMG criteria (pathogenic, likely pathogenic, VUS, likely benign, benign)
  • Evidence level for clinical statements
  • Associated diseases (ICD-10, Orphanet, OMIM)
  • Penetrance and expressivity
Therapeutic relevance
  • Drug efficacy (response/non-response)
  • Dose adjustments based on the genotype
  • Contraindications
  • Pharmacogenetic guidelines (CPIC, DPWG)
Molecular effects
  • Loss of function
  • Gain of function
  • Dominant-negative effect
  • Effect on protein folding or stability
  • Implications point to the underlying variants via derivedFrom
  • Therapeutic implications can lead to medication recommendations
  • Diagnostic implications can trigger further examinations

Evidence and sources

  • ClinVar classifications
  • Literature references (PubMed)
  • Database entries (COSMIC, dbSNP, gnomAD)
  • Expert consensus and guidelines

Molecular biomarkers

Overview: molecular biomarkers

Molecular biomarkers are aggregated genomic or molecular measures that allow prognostic or predictive statements about the course of a disease and the response to therapy. All biomarker profiles inherit from the Clinical Genomics STU3 Molecular Biomarker profile.

Currently defined profiles (not exhaustive)

Microsatellite instability (MSI): marker for DNA mismatch repair deficiency, important for immunotherapy decisions.

Mutational burden (TMB): total number of somatic mutations per megabase, a predictor of the response to checkpoint inhibitors.

Polygenic risk score (PRS): combined assessment of multiple genetic variants for risk stratification (based on RiskAssessment).

Extensibility

The Molecular Biomarker profile is flexibly extensible and is already being used for further analyses:

Further specified in the Molecular Tumor Board (MTB) module
  • Immunohistochemistry (IHC): generic Observations, dedicated profiles for PD-L1 expression, HER2 status
  • In situ hybridization (ISH): e.g. FISH for gene amplifications
  • Homologous recombination deficiency (HRD): including sub-scales
Further possible biomarkers without a specific gene assignment
  • Chromosomal instability (CIN)
  • Clonal hematopoiesis (CHIP)
  • Liquid biopsy markers (ctDNA fraction)
  • Methylation signatures
  • All biomarkers inherit from the STU3 molecular-biomarker profile
  • They reference the underlying GenomicStudy via partOf
  • They can come from different analysis methods (NGS, IHC, ISH)
  • They are included in the DiagnosticReport as result

Therapy recommendations

Overview: therapy recommendations

Therapy recommendations document the concrete courses of action that follow from the genetic findings. These Task-based profiles allow recommendations to be passed on in a structured form.

Core profiles: therapy recommendations

Medication recommendation: pharmacogenetically justified recommendations on the choice and dosing of medication.

Recommended follow-up action: further diagnostic or preventive measures based on the genetic findings.

Medication recommendation

  • Choice of medication based on the genotype
  • Dose adjustments or contraindications
  • Evidence base: CPIC, DPWG, PharmGKB
  • Examples: CYP2D6, TPMT, DPYD, HLA-B*57:01
  • Family testing in hereditary diseases
  • Presentation to a tumor board
  • Intensified screening
  • Genetic counselling
  • Follow-up examinations
  • Tasks point to the implications via reasonReference
  • The DiagnosticReport references Tasks via the recommended-action extension
  • Task status tracking: draft → requested → completed

Methodology of the genomic examination

Overview: methodology

The methodology profiles document the technical details of the genetic analyses performed, from sample processing through to the bioinformatic evaluation.

Core profiles: methodology

GenomicStudy: the overarching study that brings together all analyses for one sample (replaces UntersuchteRegion from STU2, plus more extensive methodology information and workflow IDs).

GenomicStudyAnalysis: individual analysis steps within a study (e.g. library prep, sequencing, bioinformatics).

Important components: methodology

Regions studied
  • Genes and gene panels (HGNC)
  • Genomic coordinates
  • Transcripts (MANE preferred)
  • Callable/non-callable regions
Method documentation
  • Sequencing technology (WGS, WES, panel)
  • Instruments and kits
  • Software pipelines and versions
  • Quality parameters
Quality metrics
  • Coverage (mean, median)
  • Sequencing depth
  • Q30 scores
  • Percentage of callable regions

Migration from STU2

UntersuchteRegion (old) → GenomicStudy (new)

  • Extended metadata
  • Hierarchical representation of the workflow
  • Better documentation of the instruments
  • Structured quality metrics
  • The GenomicStudy is referenced from the DiagnosticReport via an extension
  • Observations (variants) point to the GenomicStudy via partOf
  • GenomicStudyAnalysis is embedded in GenomicStudy as an extension
  • Specimen references for assigning the sample

Implementation notes: methodology

  • Minimal implementation: only the genes/regions studied
  • Extended implementation: complete workflow documentation
  • Research projects use the extended metrics
  • Routine diagnostics focus on the basic information

Family history

Overview: family history

The family history records genetically relevant diseases in blood relatives and is essential for interpreting hereditary variants and for risk assessment.

Core profile: family history

FamilyMemberHistory: documents diseases of family members with detailed information about the relationship.

Important components: family history

Relationship
  • Degree of relationship (1st, 2nd, 3rd degree)
  • Type of relationship (biological, adopted)
  • Family line (maternal, paternal)
  • Specific relationship (mother, father, sibling, etc.)
Disease documentation
  • Diagnoses (ICD-10, Orphanet, OMIM)
  • Age at onset
  • Course of the disease
  • Cause of death (where applicable)

Extensions (MII-specific)

Three dedicated extensions extend the standard resource:

  • Verwandtschaftsgrad: degree of biological relationship
  • Verwandtschaftsverhältnis: type of relationship (biological/adopted)
  • Familiäre Linie: maternal or paternal side

For details see Extensions

Clinical significance of the family history

  • Identification of hereditary patterns
  • Risk stratification for carriers
  • Establishing the indication for extended diagnostics
  • Family counselling and cascade screening
  • References the index patient via patient
  • Can point to genetic findings via reasonReference
  • Is used in the ServiceRequest as reasonReference for the test indication