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 (e.g., My Knowledge Base).

You can filter by other diseases or by summary. When filtering by summary for guideline evidence, specify the website (for example, 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 (e.g., My Knowledge Base).

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 (for example, 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
Column	Description
Published 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 (for example, 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.

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 are 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

Jackson Clinical Knowledge Base (JAX-CKB)

Connected Insights provides the Jackson Clinical Knowledge Base (JAX-CKB). For more information, refer to the Jackson CKB website.

The following from JAX-CKB are 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 are 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