Interpret a Biomarker
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Connected Insights allows users to create biomarker interpretation records (assertions). Created assertions are stored in a private database, called My Knowledge Base.
Create Assertions:
Create assertions from scratch, by editing external knowledge base assertions, or by batch-uploading existing assertions.
Create four types of assertions: biological, actionability, clinical trials, and gene descriptions
Collaboration and Management:
Store assertions in a private database, My Knowledge Base.
Collaborate on interpretation with assigned roles.
Manage assertions (view, filter, edit, approve, archive) within or outside specific cases.
Refer to for more details.
Reporting:
Include biomarker assertions in reports individually.
Include biomarker assertions in reports through automation. Refer to for more details.
Highlight biomarkers as hereditary risk findings. Refer to
For clinical trials and gene descriptions, refer to or for more details.
From scratch:
Navigate to the Biomarker Details page.
Click Create New Assertion in the top-right corner or under the list of reported assertions.
In the Classification tab, add information to the fields described below.
From an external knowledge base:
Find an assertion from an external knowledge base (e.g., CKB).
Select the specific assertion and choose Copy to new assertion from the menu next to Report.
Add and edit information in the fields described below.
By batch upload existing assertions:
The Level field describes the specificity of the assertion. It indicates whether the assertion is related to a specific variant, a group of variants, genomic region, and other factors.
Nucleotide
Specific assertion for genome build, chromosome, position, reference allele, and alternate allele. Available for small variants with transcript annotation.
Amino Acid
Specific assertion for amino acid. Available for small variants with HGVSP annotation.
Codon
Specific assertion for codon. Available for small variants with HGVSP and missense consequence annotation.
Exon
Specific assertion for exon. Available for small variants and copy number variants with exon annotation.
Gene
Specific assertion for gene. Available for small variants with gene annotation.
Annotation Overlap
Specific assertion for genome build and genomic range. Available for large variants and RNA splice variants.
Partial Fusion
Specific assertion for at least one gene. Available for RNA fusion variants.
Exact Fusion
Specific assertion for gene, fusion gene, and fusion directionality. Available for structural variants and RNA fusion variants with a fusion gene.
The Consequences field further indicates the specificity of the assertion.
For example, if you are creating an assertion for an EGFR exon 19 deletion, regardless of the specific nucleotide change, the assertion can be specified as follows:
Level: Exon
Consequence: Inframe deletion
The following consequences are available:
Gain of function variant
Loss of function variant
Transcript consequences
When assertions are matched to variants, the consequences field is matched using an OR logic.
For example, if an assertion has the stop gained, start lost, and frame shift variant consequences, it can be matched to any variant that has at least one of those consequences.
For biological assertions, if the gain of function variant or loss of function variant is specified, this variant is annotated with these consequences in future cases or if you refresh the case assertions.
If a variant is annotated with these consequences, then the relevant assertions are shown (e.g., evidence for activating mutations).
The Status field indicates the status of TMB, MSI, and GIS that the assertion is applicable to.
The following categories are available:
TMB-High
TMB-Low
MSI-High
MS-Stable
GIS-High
GIS-Low
The HRD field indicates if the assertion is related to HRD for GIS and BRCA1 and BRCA2 variants.
The following categories are available:
Undetermined
Positive
Negative
The Type field indicates whether the assertion describes the variant's biological classification or actionability.
The following selections are available:
Biological
Therapeutic
Prognostic
Diagnostic
The Direction field indicates the overall observation for the evidence the assertion is describing.
The following selections are available for therapeutic assertions:
Responsive
Non-Responsive
Contraindicated
The following selections are available for prognostic assertions:
Favorable
Unfavorable
The Therapy field indicates the therapy context for the assertion. This field is only available for therapeutic assertions.
To add a drug, search for drug names using RxNorm terms.
For assertions with drug combinations, select more than one drug in the same assertion. For assertions with a single drug, select one drug per assertion.
The Disease field indicates the disease context for the assertion.
Diseases can be searched using SNOMEDCT terms.
For Biological assertions, the default selection is neoplastic disease.
For all other assertions, the default is the disease of the case.
The Classification field is used to specify the biological or actionability classification.
For biological assertions:
Available selections are Oncogenic, Likely Oncogenic, Pathogenic, Likely Pathogenic, VUS, Likely Benign, and Benign.
For actionability assertions:
The default selections are based on Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists.
The Summary field is a free text field for an assertion summary. The summaries are displayed in the report.
The Notes field is a free text field for internal notes related to the assertion. The notes are not displayed in the report.
Reports can indicate hereditary risk findings to list variants suspected or confirmed to be of germline origin that could be associated with hereditary cancer risk. To indicate a variant is a hereditary risk finding in the report:
Navigate to the Biomarker Details page.
Create or report at least one assertion.
Select the Also report as a hereditary risk finding? checkbox that appears in the top-right corner.
Navigate to the page.
Refer to for more details.
To set up your own classification categories, following the guidance in
The Approval Status field indicates the assertion approval status. See for more details.