Connected Insights allows users to create variant 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 Manage Assertions for more details.
Reporting:
Include variant assertions in reports individually.
Include variant assertions in reports through automation. Refer to Report Automation for more details.
Highlight variants as hereditary risk findings. Refer to Report a Variant as Hereditary Risk Finding
For clinical trials and gene descriptions, refer to Create Clinical Trials or Create Gene Descriptions 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:
Navigate to the Biomarker Details page.
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:
Refer to Assertion Upload for more details.
The Level field describes the genomic change for the assertion. It indicates whether the assertion is related to a specific variant, a group of variants, genomic region, and other factors.
The Consequences field further indicates the applicability 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.
To set up your own classification categories, following the guidance in Custom Actionability Classification
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.
The Approval Status field indicates the assertion approval status. See Manage Assertions for more details.
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.
| Level | Description |
|---|---|
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.
Users can create clinical trial records when they need to add a clinical trial or edit information about a clinical trial present in an external knowledge base.
Two ways to create clinical trials: from scratch or by editing external knowledge base assertions.
From scratch:
Navigate to the Biomarker Details page.
Select Create New Assertion in the top-right corner or under the list of variant assertions to be included in the report.
In the Clinical Trial tab, add information to the fields described below.
From an external knowledge base:
Navigate to the Biomarker Details page.
Select a clinical trial from an external knowledge base (e.g., CKB).
Select Copy to new assertion in the menu next to "Report".
Add and edit information in the fields described below.
For more information, refer to Interpret a Variant.
For more information, refer to Interpret a Variant.
The Status field describes 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 Title field indicates the clinical trial title.
The Registry field indicates the clinical trial registry (e.g., https://clinicaltrials.gov/).
The Registry ID field indicates the clinical trial registry identifier (e.g., NCT1234).
The Phase field indicates the phase of the clinical trial (e.g., Phase III).
The External Link indicates the URL for the clinical trial record online.
For more information, refer to Interpret a Variant.
The Location field indicates the city, state, and country of the clinical trial.
Multiple locations can be added.
Country is required.
The Approval Status field indicates the assertion approval status. See Manage Assertions for more details.
My Knowledge Base is a private database where all created assertions are stored.
Users can view, edit, collaborate on, archive/unarchive, track changes, and view reports for assertions.
Access all My Knowledge Base assertions via My Knowledge Base using the app selector (grid icon) in the top-right.
Explore variant interpretations, gene descriptions, and other assertions under respective tabs.
Apply filters for specific searches and click the arrow on the left side of the assertion for details information and history.
To download assertions, select + New Assertion and then Download to view.
Edit My Knowledge Base assertions directly on the Biomarker Details page within a case or through My Knowledge Base.
Update necessary fields and set the approval status to Draft, Pending Approval, or Approved.
Refer to Interpret a Variant, Create Clinical Trials, or Create Gene Descriptions for field descriptions.
Use assertion statuses to manage the collaborative approval process.
Draft: For incomplete interpretations or those created by users without approval rights (i.e., case manager - curator).
Pending Approval: When assertions are ready for review.
Approved: After assertions have been reviewed and confirmed.
Archived: To remove assertions from active use while keeping them for records.
A report cannot be approved if reported assertions have statuses Draft, Pending Approval, or Archived.
If a reported assertion has Draft or Pending Approval status, an icon accompanies the assertion on key pages. A figure below shows a draft assertion in the Overview page, Biomarker Details page and in the assertion form.
Archiving is used to remove My Knowledge Base assertions from active use while keeping them for records. Archived assertions are not displayed in the Overview, Variants, and Biomarker Details pages, and cannot be added to the report.
To archive an assertion while working on a specific case:
Find a My Knowledge Base assertion on the Biomarker Details page.
Select Archive in the menu to the left of "Report".
To archive an assertion outside of a specific case:
Navigate to My Knowledge Base using the app selector (grid icon) in the top-right.
Find the assertion you want to archive by searching or filtering.
Select Archive in the menu on the right side.
To unarchive an assertion:
Navigate to My Knowledge Base using the app selector (grid icon) in the top-right.
Find the archived assertion you want to unarchive by searching or filtering.
Select Unarchive in the menu on the right.
Case Manager - Curator can assign all statuses, except for approved and archived.
Case Manager can assign all statuses, except for archived.
Lab Director can assign all statuses.
Administrator (Connected Insights - Local) can assign all statuses.
A gene description summarizes gene function and its association with diseases.
It provides context for variant interpretation and often appears before the variant summary in reports.
Users can create gene descriptions separately from variants in their knowledge base.
Users can create gene descriptions from scratch or based on external knowledge bases.
These descriptions automatically apply to all variants within a gene.
Collaborative editing and approval processes are available. See for more details.
To create from scratch:
Go to the Biomarker Details page.
Click Create New Assertion.
In the Gene Description tab, specify the gene role (e.g., Oncogene or Tumor Suppressor), provide a summary, and set the approval status.
Curating gene roles helps with variant interpretation (i.e., providing input for oncogenicity prediction).
From an external knowledge base:
Navigate to the Biomarker Details page.
Choose a gene description from an external knowledge base (e.g., CKB).
Select Copy to new assertion in the menu next to "Report".
Edit the fields as needed.