Propositions (Steps 2--6)

Overview

Steps 2--6 of gks_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.

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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

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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

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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

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Step 5: Primary Proposition

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

Field	Description
type	Proposition type from Step 1 mapping (e.g., VariantPathogenicityProposition)
subjectVariant	Reference to the categorical variant via clinvar:{variation_id}
predicate	Predicate from Step 1 mapping (e.g., isCausalFor, isOncogenicFor)
objectCondition_single	Single condition from the condition pipeline
objectCondition_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_gks_scv_proposition -- one row per SCV with fully assembled proposition. Internal

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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)
subjectVariant	JSON pointer 4/proposition/subjectVariant referencing the parent proposition's variant
predicate	Target predicate (e.g., associatedWithBetterOutcomeFor, predictsSensitivityTo)
objectTherapy_single	Single drug therapy for therapeutic assertions
objectTherapy_compound	Compound therapy for multi-drug therapeutic assertions
conditionQualifier	Condition moved to qualifier position for therapeutic assertions (since objectCondition becomes the therapy)
geneContextQualifier	Gene concept from Step 2
modeOfInheritanceQualifier	Mode of inheritance from Step 3

The JSON pointer 4/proposition/subjectVariant 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_gks_scv_target_proposition -- one row per somatic SCV with target proposition. Internal

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Dependencies

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