Statement

Trial Use

May change in future releases. See Maturity Model.

Computational Definition

A claim of purported truth as made by a particular agent, on a particular occasion. Statements may be used to put forth a possible fact (i.e. a ‘Proposition’) as true or false, or to provide a more nuanced assessment of the level of confidence or evidence supporting a particular Proposition.

Information Model

Some Statement attributes are inherited from Information Entity.

Field	Flags	Type	Limits	Description
id		string	0..1	The ‘logical’ identifier of the Entity in the system of record, e.g. a UUID. This ‘id’ is unique within a given system, but may or may not be globally unique outside the system. It is used within a system to reference an object from another.
type		string	1..1	MUST be “Statement”.
name		string	0..1	A primary name for the entity.
description		string	0..1	A free-text description of the Entity.
aliases	⋮	string	0..m	Alternative name(s) for the Entity.
extensions	⋮	Extension	0..m	A list of extensions to the Entity, that allow for capture of information not directly supported by elements defined in the model.
specifiedBy		Method | iriReference	0..1	A specification that describes all or part of the process that led to creation of the Information Entity
contributions	↓	Contribution	0..m	Specific actions taken by an Agent toward the creation, modification, validation, or deprecation of an Information Entity.
reportedIn	⋮	Document | iriReference	0..m	A document in which the the Information Entity is reported.
proposition		Proposition | iriReference	1..1	A possible fact, the validity of which is assessed and reported by the Statement. A Statement can put forth the proposition as being true, false, or uncertain, and may provide an assessment of the level of confidence/evidence supporting this claim.
direction		string	1..1	A term indicating whether the Statement supports, disputes, or remains neutral w.r.t. the validity of the Proposition it evaluates.
strength		Mappable Concept | iriReference	0..1	A term used to report the strength of a Proposition’s assessment in the direction indicated (i.e. how strongly supported or disputed the Proposition is believed to be). Implementers may choose to frame a strength assessment in terms of how confident an agent is that the Proposition is true or false, or in terms of the strength of all evidence they believe supports or disputes it.
quality	D	Mappable Concept | iriReference	0..1	A term used to report the quality of the assessment of a Proposition taking into consideration the reliability of the method, the contributor’s self-reporting of the rigor of the evaluation, and the overall robustness of the supporting or disputing evidence. This is useful when there is a consistent policy and authority that manages and a governing framework for evaluating the quality of evidence. Also known as trust rating, review status or ranking.
score	D	number	0..1	A quantitative score that indicates the strength of a Proposition’s assessment in the direction indicated (i.e. how strongly supported or disputed the Proposition is believed to be). Depending on its implementation, a score may reflect how confident that agent is that the Proposition is true or false, or the strength of evidence they believe supports or disputes it. Instructions for how to interpret the meaning of a given score may be gleaned from the method or document referenced in ‘specifiedBy’ attribute.
classification		Mappable Concept | iriReference	0..1	A single term or phrase summarizing the result of direction and strength assessments of a Statement’s Proposition, in terms of a classification of its subject.
hasEvidence	⋮	Statement | Study Result | Data Item | iriReference	0..m	An individual piece of information that was evaluated as evidence in assessing the validity of the Proposition put forth by the Statement.
hasEvidenceLines	⋮	Evidence Line | iriReference	0..m	An evidence-based argument that supports or disputes the validity of the proposition that a Statement assesses or puts forth as true. The strength and direction of this argument (whether it supports or disputes the proposition, and how strongly) is based on an interpretation of one or more pieces of information as evidence (i.e. ‘Evidence Items).

Inherits: Information Entity

Used in: Variant Clinical Significance Statement (AAC 2017), Variant Oncogenicity Statement (CCV 2022), Variant Pathogenicity Statement (ACMG 2015)

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Data Structure

Statements represent assertions or assessments of general knowledge about a variant - e.g. an assertion that ‘HRAS:c.173C>T is pathogenic for Costello Syndrome, or an assessment that there is presently only moderate evidence supporting this possible fact.

In VA-Spec, the Statement class and its profiles can support the general data structure below.

Legend A class-level view of the Statement-based structures supported in VA-Spec data, including the classes that describe provenance (Proposition, Method, Contribution, Document) and evidence (Evidence Line, Study Result, Data Item).

In this structure:

• A Statement roots a central axis where it is linked, via hasEvidenceLines, to zero or more Evidence Lines - discrete arguments for or against it - and/or, via hasEvidence, directly to a Study Result, Data Item, or prior Statement used as evidence.

• Each Evidence Line may in turn be linked, via hasEvidenceItems, to zero or more pieces of information (e.g. Study Results) that were used to build its evidence-based argument.

• The Proposition contained in the Statement object encapsulates a structured representation of the possible fact that the Statement may assert or assess (e.g. that ‘HRAS:c.173C>T is causal for Costello Syndrome’). Unless otherwise stated, this is the same proposition against which evidence is assessed in supporting Evidence Lines.

• Surrounding this central axis are classes that describe the provenance of the central artifacts, including Contributions made to them by Agents, Methods that specify their creation, and Documents that describe them.

A data example illustrating this structure for a Variant Pathogenicity Statement can be found here.

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Implementation Guidance

1. Statement and Proposition Semantics

Statements put forth a Proposition that expresses some possible fact about the world, and may provide an assessment of this proposition’s validity (e.g. a level of confidence that it is true, or indicator of the overall strength of evidence supporting it). The semantics of the Proposition are captured in subject, predicate, and object attributes, plus optional, type-specific qualifiers (SPOQ; see the guidance on qualifiers below). An assessment of the Proposition’s validity can be captured using direction, strength, and/or score attributes (DS).

• The direction attribute is used to indicate whether the Statement’s Proposition is supported by the agent’s assessment (when evidence favors its validity), is disputed by the agent’s assessment (when evidence argues against its validity), or remains neutral (when conflicting or insufficient evidence exists to assert one direction or the other). Values come from an enumerated set of strings defined in the model {‘supports’, ‘disputes’, ‘neutral’}.

• The strength attribute is used to report the strength of this assessment in the direction indicated. Strength can be framed as a level of confidence that the Proposition is true or false, or as a strength of evidence that supports or disputes it - depending on what values of this attribute are used (e.g. ‘high confidence’, ‘low confidence’, etc. if confidence level is being assessed, or ‘strong evidence’, ‘weak evidence’, etc. if evidence strength is being assessed). ALternatively, data providers can choose values that don’t commit to one or the other if they don’t want to make the distinction (e.g. ‘high’ vs ‘medium’ vs ‘low’).

• The score attribute serves the same purpose as strength, but allows for a quantitative assessment based on a numerical score, and can be used in addition to or as an alternative to the ‘strength’ attribute.

This ‘SPOQ-DS’ Proposition pattern is used to explicitly represent the semantics of the central piece of knowledge reported in any Statement, which is supported by evidence and provenance information captured in other Statement attributes.

2. Attaching Evidence to a Statement

A Statement can cite the evidence behind its assessment in two complementary ways:

• hasEvidence links the Statement directly to information used as evidence - a Study Result, Data Item, or prior Statement (or an IRI reference to one of these). Use this when the data simply records that some information was used as evidence. (Structured, scored arguments are attached instead via hasEvidenceLines, below.)

• hasEvidenceLines links the Statement to one or more Evidence Lines - discrete, scored, directional arguments (each with its own targetProposition, directionOfEvidenceProvided, strengthOfEvidenceProvided, and evidenceOutcome) built from the information they assessed. Use this when the data captures how information was interpreted and scored as an argument.

See the Evidence Line page for when to use a structured Evidence Line rather than citing evidence directly, how deeply Evidence Lines nest, and how broadly to scope each argument.

3. Use of Qualifiers (the “Q” in SPOQ):

• Qualifiers let a Proposition represent more complex, n-ary claims that a simple subject-predicate-object (SPO) triple cannot capture on its own. For example, where an SPO triple asserts that ‘Variant X’ - predicts sensitivity to - ‘Treatment Y’, a qualifier can restrict that claim to the context of a particular ‘Disease Z’. Qualifiers can also quantify a claim - e.g. an SPO triple reporting that ‘Variant X’ - causes - ‘Phenotype Y’ can carry penetrance information indicating the percentage of carriers in which the phenotype manifests.

• The Q in SPOQ is conceptual, not a physical attribute. The core Proposition class does not define a qualifier property, and there is no Qualifier class - so no Proposition instance ever carries a field literally named qualifier. Qualifiers come into being only when a concrete Proposition subclass is formally defined and declares them.

• When a Proposition type defines qualifiers, each one is declared as its own named attribute using the xxxQualifier convention, where xxx names the kind of qualifying information it carries (e.g. geneContextQualifier, alleleOriginQualifier, conditionQualifier, penetranceQualifier). Declaring each qualifier as a distinct named attribute keeps the data succinct and parsable, and lets the schema apply and validate constraints specific to that qualifier.

• A single Proposition type may define more than one qualifier, and each may be required or optional according to that type’s definition. For example, Variant Pathogenicity Proposition defines geneContextQualifier, alleleOriginQualifier, penetranceQualifier, and modeOfInheritanceQualifier (all optional), while Variant Therapeutic Response Proposition defines geneContextQualifier and alleleOriginQualifier (optional) together with a required conditionQualifier.