Actionability

Diagnostic

A single table in the biomarker details provides a list of all the diagnostic assertions from all included sources that have content about the biomarker (i.e., My Knowledge Base, OncoKB, CKB, CIViC).

If you have existing knowledge to upload to the system, refer to Upload Assertions.

You can filter by other diseases or by summary. When filtering by summary for guideline evidence, specify the website (e.g., ESMO.org or NCCN.org). Filter changes are saved and applied across variants within a case and can be reset if needed.

Therapeutic, Prognostic

A single table in the biomarker details provides a list of all the therapeutic and prognostic assertions from all included sources that have content about the biomarker (i.e., My Knowledge Base, OncoKB, CKB, CIViC).

If you have existing knowledge to upload to the system, refer to Upload Assertions.

By default, the assertions are filtered by the case and ancestor diseases. Ancestor diseases are determined using SNOMEDCT. These diseases can be viewed at the SNOMED CT Browser website, with the following exceptions:

• Descendents of neoplastic disease do not include ancestors beyond neoplastic disease.

• Non-small cell lung cancer has been added as an ancestor of adenocarcinoma of lung.

You can filter by other diseases, by summary, or by approval. When filtering by summary for guideline evidence, specify the website (e.g., ESMO.org or NCCN.org). Filter changes are saved and applied across variants within a case and can be reset if needed.

Actionability Legend

Field Name	Description
Directional Arrows	Opens to view the assertion summary.
Update Date	The date that the assertion was updated.
Source	Knowledge base origin of the assertion.
Biomarker	Indicates whether an assertion is the nucleotide, annotation overlap, partial fusion, amino acid, codon, exon, or gene level. This column is only available for variants.
Status	Indicates the TMB, MSI, or GIS status for the assertion. This column is available for TMB, MSI, and GIS.
HRD	Indicates whether an assertion is associated with HRD positive or negative. This column is available for GIS and variants when the selected transcript is for BRCA1/2.
Classification	This column displays the classification (e.g., Tier 1A), as indicated by the knowledge base.
Type	Therapeutic, Diagnostic, or Prognostic as indicated by the knowledge base.
Direction	• For therapeutic; responsive, nonresponsive, etc., as indicated by the knowledge base. • For prognostic; favorable, unfavorable, etc., as indicated by the knowledge base.
Therapy	Therapy for the assertion.
Disease	Disease for the assertion.
Approval	Authorities that have approved the therapy for the biomarker and disease. • CKB provides FDA, EMA, ANVISA, PDMA, and TGA approvals. • OncoKB level 1 assertions are annotated with FDA.
Actions	This column contains the following available actions: • Add to report* • Archive, if the assertion is in My Knowledge Base • Copy to New Assertion, if the assertion is not in My Knowledge Base • View past cases To edit an assertion, add it to the report before editing. For more information, refer to Manage Assertions.

*Classification Mapping

When reporting an assertion that is not from My Knowledge Base (e.g., OncoKB), classifications will be reported using your Actionability Classifications. If you are using AMP/ASCO/CAP, classifications will be adjusted as follows:

Connected Insights	OncoKB	CKB	CIViC
Tier 1A	Level 1 Level R1 Level Px1 Level Dx1 Level 2 Level Px2 Level Dx2	Tier 1A	Level A
Tier 1B	Level 3A Level Px3 Level Dx3	Tier 1B	Level B
Tier 2C	Level 3B	Tier 2C	Therapeutic Level C
Tier 2D	Level 4 Level R2	Tier 2D	Non-therapeutic Level C Level D Level E

Available Knowledge Bases

Memorial Sloan Kettering OncoKB

Connected Insights provides the Memorial Sloan Kettering OncoKB. For more information, refer to the OncoKB website.

The following from OncoKB is not supported:

• Non-compliant HGVS

• Unspecified positions: Epigenetic Silencing, ARv567es, AR-V7, DNMT3B7, vIII, vII, vV, TGFBR1*6A, Overexpression, Wildtype, Promoter Hypermethylation, Hypermethylation, Kinase Domain Duplication, Internal Tandem Duplication, Partial Tandem Duplication

Genomenon Cancer Knowledge Base (CKB)

Connected Insights provides the Genomenon Cancer Knowledge Base (formerly Jackson Laboratory Clinical Knowledge Base). For more information, refer to the Genomenon CKB website.

The following from CKB is not supported:

• Complex molecular profiles (for example, co-occuring biomarker assertions)

• Emerging and risk factor evidence types

• Class #, over exp, dec exp, hypermethylation, hypomethylation, dup exonX, dup exonX-X, LOH, loss, negative (except for HRD andMSI), positive (except for HRD), and wild type variants.

Clinical Interpretation of Variants in Cancer (CIViC)

Connected Insights also provides the Clinical Interpretation of Variants in Cancer (CIViC) knowledge base. For more information, refer to the CIViC website.

The following from CIViC is not supported:

• Assertions

• Functional and oncogenic evidence types

• Splice Site (c.3028G>A), Boolean-like evidence (for example, (V600E or V600K) and Amplification), Underexpression, Overexpression, Expression, Decreased Peri-therapeutic Expression, Cytoplasmic Expression, Loss, Biallelic Inactivation, Alu Insertion, Alternative Transcript, RSID, Homozygosity, Copy-neutral Loss of Heterozygosity, Cytoplasmic Mislocation, Deleterious Mutation, Double Ph, Wildtype, Domain, Exon-specific fusions