AMP/ASCO/CAP 2017 Aligned Profiles

The following profiles align with terminology and curation conventions from the 2017 AMP/ASCO/CAP Clinical Variant Interpretation Guidelines.

These initial profiles were developed to support the following implementations and use cases:

Implementer	Use Case
VICC MetaKB	Using VA-Spec models to structure diagnostic, prognostic, and therapeutic response variant classifications and evidence in its community-facing data exchange APIs.
ClinVar Submission Utility	Uses VA-Spec as input format for submission tools that send variant classifications and evidence from CIViC to the ClinVar database via its API.

The number and coverage of these profiles will grow as these implementations expand their scope, and additional adopters bring new use cases to the spec.

Variant Clinical Significance Statement (AAC 2017)

Draft

May change significantly in future releases. See Maturity Model.

Computational Definition

A statement reporting a conclusion from a single study about the clinical significance of a variant with respect to a condition, based on interpretation of the study’s results.

Information Model

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	1..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		Variant Clinical Significance 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	0..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	The strength of support that the Statement is determined to provide for or against the Variant Clinical Significance Proposition for the assessed variant, based on the curation and reporting conventions of the AMP/ASCO/CAP 2017 Guidelines.
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	1..1	A single term or phrase classifying the subject variant based on the outcome of direction and strength assessments of the Statement’s Proposition, using terms from the AMP/ASCO/CAP 2017 Guidelines.
hasEvidence	⋮	Information Entity | 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).

Additional Constraints

If property…	has value…	then property…	must…
classification.primaryCoding.code	tier i	hasEvidenceLines	be one of: iriReference, Variant Diagnostic Evidence Line (AAC 2017), Variant Prognostic Evidence Line (AAC 2017), Variant Therapeutic Evidence Line (AAC 2017)
classification.primaryCoding.code	tier i	classification.name	have value Tier I
classification.primaryCoding.code	tier i	strength.primaryCoding.code	have value strong
classification.primaryCoding.code	tier i	direction	have value supports
classification.primaryCoding.code	tier ii	hasEvidenceLines	be one of: iriReference, Variant Diagnostic Evidence Line (AAC 2017), Variant Prognostic Evidence Line (AAC 2017), Variant Therapeutic Evidence Line (AAC 2017)
classification.primaryCoding.code	tier ii	classification.name	have value Tier II
classification.primaryCoding.code	tier ii	strength.primaryCoding.code	have value potential
classification.primaryCoding.code	tier ii	direction	have value supports
classification.primaryCoding.code	tier iii	classification.name	have value Tier III
classification.primaryCoding.code	tier iii	strength	not be provided
classification.primaryCoding.code	tier iii	direction	have value neutral
classification.primaryCoding.code	tier iv	classification.name	have value Tier IV
classification.primaryCoding.code	tier iv	strength	not be provided
classification.primaryCoding.code	tier iv	direction	have value disputes

Composes: Statement

Artifacts

• Variant Clinical Significance Statement Source Yaml

• Variant Clinical Significance Statement Json Schema

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Variant Amp/Asco/Cap Evidence Line (AAC 2017)

Draft

May change significantly in future releases. See Maturity Model.

Computational Definition

General statement for AMP/ASCO/CAP

Information Model

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 “EvidenceLine”.
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.
targetProposition		Variant Prognostic Proposition | Variant Diagnostic Proposition | Variant Therapeutic Response Proposition | iriReference	1..1	The possible fact against which evidence items contained in an Evidence Line were collectively evaluated, in determining the overall strength and direction of support they provide. For example, in an ACMG Guideline-based assessment of variant pathogenicity, the support provided by distinct lines of evidence are assessed against a target proposition that the variant is pathogenic for a specific disease.
hasEvidenceItems	⋮	Information Entity | iriReference	0..m	An individual piece of information that was evaluated as evidence in building the argument represented by an Evidence Line.
directionOfEvidenceProvided		string	1..1	The direction of support that the Evidence Line is determined to provide toward its target Proposition (supports, disputes, neutral)
strengthOfEvidenceProvided		Mappable Concept | iriReference	0..1	The strength of support that an Evidence Line is determined to provide for or against its target Proposition, evaluated relative to the direction indicated by the directionOfEvidenceProvided value.
scoreOfEvidenceProvided		number	0..1	A quantitative score indicating the strength of support that an Evidence Line is determined to provide for or against its target Proposition, evaluated relative to the direction indicated by the directionOfEvidenceProvided value.
evidenceOutcome		Mappable Concept | iriReference	0..1	A term summarizing the overall outcome of the evidence assessment represented by the Evidence Line, in terms of the direction and strength of support it provides for or against the target Proposition.

Composes: Evidence Line

Used in: Variant Diagnostic Evidence Line (AAC 2017), Variant Prognostic Evidence Line (AAC 2017), Variant Therapeutic Evidence Line (AAC 2017)

Artifacts

• Amp Asco Cap Evidence Line Source Yaml

• Amp Asco Cap Evidence Line Json Schema

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Variant Diagnostic Evidence Line (AAC 2017)

Draft

May change significantly in future releases. See Maturity Model.

Computational Definition

Diagnostic statement for AMP/ASCO/CAP

Information Model

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 “EvidenceLine”.
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.
targetProposition		Variant Diagnostic Proposition | iriReference	1..1	The possible fact against which evidence items contained in an Evidence Line were collectively evaluated, in determining the overall strength and direction of support they provide. For example, in an ACMG Guideline-based assessment of variant pathogenicity, the support provided by distinct lines of evidence are assessed against a target proposition that the variant is pathogenic for a specific disease.
hasEvidenceItems	⋮	Information Entity | iriReference	0..m	An individual piece of information that was evaluated as evidence in building the argument represented by an Evidence Line.
directionOfEvidenceProvided		string	1..1	The direction of support that the Evidence Line is determined to provide toward its target Proposition (supports, disputes, neutral)
strengthOfEvidenceProvided		Mappable Concept | iriReference	0..1	The strength of support that an Evidence Line is determined to provide for or against its target Proposition, evaluated relative to the direction indicated by the directionOfEvidenceProvided value.
scoreOfEvidenceProvided		number	0..1	A quantitative score indicating the strength of support that an Evidence Line is determined to provide for or against its target Proposition, evaluated relative to the direction indicated by the directionOfEvidenceProvided value.
evidenceOutcome		Mappable Concept | iriReference	0..1	A term summarizing the overall outcome of the evidence assessment represented by the Evidence Line, in terms of the direction and strength of support it provides for or against the target Proposition.

Composes: Variant Amp/Asco/Cap Evidence Line (AAC 2017)

Used in: Variant Clinical Significance Statement (AAC 2017)

Artifacts

• Diagnostic Evidence Line Source Yaml

• Diagnostic Evidence Line Json Schema

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Variant Prognostic Evidence Line (AAC 2017)

Draft

May change significantly in future releases. See Maturity Model.

Computational Definition

Prognostic statement for AMP/ASCO/CAP

Information Model

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 “EvidenceLine”.
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.
targetProposition		Variant Prognostic Proposition | iriReference	1..1	The possible fact against which evidence items contained in an Evidence Line were collectively evaluated, in determining the overall strength and direction of support they provide. For example, in an ACMG Guideline-based assessment of variant pathogenicity, the support provided by distinct lines of evidence are assessed against a target proposition that the variant is pathogenic for a specific disease.
hasEvidenceItems	⋮	Information Entity | iriReference	0..m	An individual piece of information that was evaluated as evidence in building the argument represented by an Evidence Line.
directionOfEvidenceProvided		string	1..1	The direction of support that the Evidence Line is determined to provide toward its target Proposition (supports, disputes, neutral)
strengthOfEvidenceProvided		Mappable Concept | iriReference	0..1	The strength of support that an Evidence Line is determined to provide for or against its target Proposition, evaluated relative to the direction indicated by the directionOfEvidenceProvided value.
scoreOfEvidenceProvided		number	0..1	A quantitative score indicating the strength of support that an Evidence Line is determined to provide for or against its target Proposition, evaluated relative to the direction indicated by the directionOfEvidenceProvided value.
evidenceOutcome		Mappable Concept | iriReference	0..1	A term summarizing the overall outcome of the evidence assessment represented by the Evidence Line, in terms of the direction and strength of support it provides for or against the target Proposition.

Composes: Variant Amp/Asco/Cap Evidence Line (AAC 2017)

Used in: Variant Clinical Significance Statement (AAC 2017)

Artifacts

• Prognostic Evidence Line Source Yaml

• Prognostic Evidence Line Json Schema

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Variant Therapeutic Evidence Line (AAC 2017)

Draft

May change significantly in future releases. See Maturity Model.

Computational Definition

Therapeutic statement for AMP/ASCO/CAP

Information Model

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 “EvidenceLine”.
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.
targetProposition		Variant Therapeutic Response Proposition | iriReference	1..1	The possible fact against which evidence items contained in an Evidence Line were collectively evaluated, in determining the overall strength and direction of support they provide. For example, in an ACMG Guideline-based assessment of variant pathogenicity, the support provided by distinct lines of evidence are assessed against a target proposition that the variant is pathogenic for a specific disease.
hasEvidenceItems	⋮	Information Entity | iriReference	0..m	An individual piece of information that was evaluated as evidence in building the argument represented by an Evidence Line.
directionOfEvidenceProvided		string	1..1	The direction of support that the Evidence Line is determined to provide toward its target Proposition (supports, disputes, neutral)
strengthOfEvidenceProvided		Mappable Concept | iriReference	0..1	The strength of support that an Evidence Line is determined to provide for or against its target Proposition, evaluated relative to the direction indicated by the directionOfEvidenceProvided value.
scoreOfEvidenceProvided		number	0..1	A quantitative score indicating the strength of support that an Evidence Line is determined to provide for or against its target Proposition, evaluated relative to the direction indicated by the directionOfEvidenceProvided value.
evidenceOutcome		Mappable Concept | iriReference	0..1	A term summarizing the overall outcome of the evidence assessment represented by the Evidence Line, in terms of the direction and strength of support it provides for or against the target Proposition.

Composes: Variant Amp/Asco/Cap Evidence Line (AAC 2017)

Used in: Variant Clinical Significance Statement (AAC 2017)

Artifacts

• Therapeutic Evidence Line Source Yaml

• Therapeutic Evidence Line Json Schema