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Propositions

A proposition defines what a statement asserts — the relationship between a variant and a condition. Each proposition follows the subject-predicate-object pattern from the GA4GH VA-Spec specification:

  • Subject (subject) — a reference to a ClinVar variation via #/variation/clinvar:{id}
  • Predicate — the relationship type (e.g., isCausalFor, isOncogenicFor)
  • Object (object) — a condition, disease, or phenotype

The ClinvarProposition union type encompasses all 13 proposition types valid in ClinVar-GKM.

Proposition Types

ClinVar-GKM uses 13 proposition types: 3 from the GA4GH VA-Spec standard and 10 defined specifically for ClinVar submission categories. The 10 ClinVar-specific types are open subtypes of the VA-Spec SubjectVariantProposition base — each carries its own real type name (the former CustomProposition + customPropositionType model is retired).

GA4GH Standard Types

These types are defined in the VA-Spec and used directly:

Code Type Predicate Description
PATH VariantPathogenicityProposition isCausalFor Germline pathogenicity/benignity
ONCO VariantOncogenicityProposition isOncogenicFor Oncogenicity classification
SCI VariantClinicalSignificanceProposition hasClinicalSignificanceFor Somatic clinical impact

ClinVar-Specific Types

These types handle ClinVar submission categories not covered by the GA4GH specifications. Several are no longer accepted as new submissions by ClinVar, but historical submissions remain in the dataset.

Code Type Predicate Description
RF ClinvarRiskFactorProposition isRiskFactorFor Risk factor
PROT ClinvarProtectiveProposition isProtectiveFor Protective
DR ClinvarDrugResponseProposition hasDrugResponseFor Drug response
AFF ClinvarAffectsProposition hasAffectFor Affects
ASSOC ClinvarAssociationProposition isAssociatedWith Association
CS ClinvarConfersSensitivityProposition confersSensitivityFor Confers sensitivity
OTH ClinvarOtherProposition isClinvarOtherAssociationFor Other
NP ClinvarNotProvidedProposition hasNoProvidedClassificationFor Not provided
CONF ClinvarConflictingDataFromSubmitterProposition isConflictingDataFromSubmittersFor Conflicting data (germline only)
UNDEF ClinvarUndefinedProposition isClinvarUndefinedAssociationFor Fallback for a classification that maps to no defined type

Somatic Evidence Line Propositions

Somatic clinical impact (SCI) statements carry evidence lines with their own target propositions. These 3 types appear only on ClinvarSomaticEvidenceLine objects, not as top-level statement propositions:

Code Type Predicates
TR VariantTherapeuticResponseProposition predictsSensitivityTo, predictsResistanceTo
DIAG VariantDiagnosticProposition isDiagnosticInclusionCriterionFor, isDiagnosticExclusionCriterionFor
PROG VariantPrognosticProposition associatedWithBetterOutcomeFor, associatedWithWorseOutcomeFor

Inherited Attributes

All ClinVar proposition types are subtypes of the VA-Spec SubjectVariantProposition (the ClinVar-specific types via the open ClinvarGermlineCustomProposition base; the standard types via VA-Spec's GeneticContextVariantProposition). Common attributes:

  • subject — the variant being classified, as a #/variation/ reference
  • object — the asserted object, as a reference: a #/condition/ or #/conditionSet/ for most types; a #/therapy/ or #/therapyGroup/ for VariantTherapeuticResponseProposition (drug therapies are content-addressed and deduplicated into the therapy / therapyGroup bundle sections)
  • conditionQualifier — for VariantTherapeuticResponseProposition, the #/condition/ or #/conditionSet/ the therapeutic response is asserted in (since object carries the therapy)
  • geneContextQualifier — the gene impacted by the variant (embedded)
  • alleleOriginQualifier — germline, somatic, or mosaic origin

See the individual class pages for the complete information model including all inherited fields.