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Propositions (Steps 2--6)

Overview

Steps 2--6 of gkm_scv_statement_proc build the qualifier tables and assemble the primary and target propositions for each SCV. Qualifiers capture gene context, mode of inheritance, and penetrance; propositions combine the variant, condition, and qualifiers into the structured assertion that forms the core of each VA-Spec Statement.

Steps 2--4: Qualifier Tables

Step 2: Build temp_gene_context_qualifiers

Extracts gene context from single_gene_variation by matching each SCV's variation_id to its associated gene. For each match, builds a gene concept with:

  • conceptType: "gene"
  • primaryCoding: NCBI Gene identifier using both identifiers.org and NCBI Gene URLs
  • HGNC mappings: When an HGNC identifier is available, included as an additional coding
  • submittedGeneSymbols extension: Gene symbols from clinical_assertion_variation, preserving the submitter's original gene annotations

When no single-gene match exists for a variation, the qualifier falls back to a record noting that "submitted genes were not normalized."

Output: temp_gene_context_qualifiers -- one row per SCV+gene combination. Internal

Step 3: Build temp_moi_qualifiers

Extracts ModeOfInheritance from assertion attributes in clinical_assertion. When a matching HPO term is available, the qualifier includes a primaryCoding with the HPO term identifier and label. All qualifiers include a submittedModeOfInheritance extension preserving the original submitted value.

Output: temp_moi_qualifiers -- one row per SCV with mode of inheritance. Internal

Step 4: Build temp_penetrance_qualifiers

Derives penetrance qualifiers for specific classification types:

Classification Category Penetrance Value
Pathogenic-low penetrance (p-lp), Likely pathogenic-low penetrance (lp-lp) "low"
Established risk allele (era), Likely risk allele (lra), Uncertain risk allele (ura) "risk"

Each penetrance qualifier includes a submittedClassification extension preserving the original classification label that triggered the penetrance derivation.

Output: temp_penetrance_qualifiers -- one row per qualifying SCV. Internal

Step 5: Primary Proposition

Assembles the SCV proposition by joining temp_gkm_scv with all qualifier tables and condition sets from gkm_scv_condition_sets. The resulting proposition contains:

Field Description
type Proposition type from Step 1 mapping (e.g., VariantPathogenicityProposition)
subject Reference to the categorical variant via clinvar:{variation_id}
predicate Predicate from Step 1 mapping (e.g., isCausalFor, isOncogenicFor)
object_single Single condition from the condition pipeline
object_compound ConditionSet for SCVs with multiple conditions
geneContextQualifier Gene concept from Step 2
modeOfInheritanceQualifier Mode of inheritance from Step 3
penetranceQualifier Penetrance from Step 4

Output: temp_gkm_scv_proposition -- one row per SCV with fully assembled proposition. Internal

Step 6: Target Proposition (Somatic)

Builds the evidence line target proposition for somatic clinical impact assertions. This proposition uses the evidence_line_target_proposition type and predicate derived in Step 1 and adds somatic-specific fields:

Field Description
type Target proposition type (e.g., VariantPrognosticProposition, VariantTherapeuticResponseProposition)
subject JSON pointer 4/proposition/subject referencing the parent proposition's variant
predicate Target predicate (e.g., associatedWithBetterOutcomeFor, predictsSensitivityTo)
object For therapeutic assertions, a reference to the therapy: #/therapy/clinvar.therapy:{sha256} for a single drug, or #/therapyGroup/clinvar.therapygroup:{sha256} for a multi-drug combination. Therapies are extracted (temp_gkm_scv_therapy), content-addressed, and deduplicated into the gkm_dict_therapy / gkm_dict_therapygroup dictionaries; a TherapyGroup's concepts reference its member therapies via #/therapy/
conditionQualifier Condition moved to qualifier position for therapeutic assertions (since object becomes the therapy), as a #/condition/ or #/conditionSet/ reference
geneContextQualifier Gene concept from Step 2
modeOfInheritanceQualifier Mode of inheritance from Step 3

The JSON pointer 4/proposition/subject is used instead of duplicating the variant reference, linking the target proposition back to the same variant defined in the parent (Step 5) proposition.

Output: temp_gkm_scv_target_proposition -- one row per somatic SCV with target proposition. Internal

Dependencies

  • Source Tables: single_gene_variation, clinical_assertion, clinical_assertion_variation, gene
  • Lookup Tables: hpo_terms
  • Upstream Steps: Step 1 (temp_gkm_scv), condition pipeline (gkm_scv_condition_sets)