> For the complete documentation index, see [llms.txt](https://help.connected.illumina.com/llms.txt). Markdown versions of documentation pages are available by appending `.md` to page URLs; this page is available as [Markdown](https://help.connected.illumina.com/connected-insights/resources-and-references/rar-release-notes/5.4-release-notes.md).

# 5.4 Release Notes

These release notes include new features, product limitations, and known issues for Connected Insights 5.4.

## New Features

### Compatibility

* **New Pipeline Support** - Added support for TSO 500 ctDNA v2.6.4 (including GRCh38), [DRAGEN WGS MRD v4.4.6](https://app.gitbook.com/s/g4X7574yYTwAebYcyGXr/product-guides/dragen-v4.4/mrd), and DRAGEN v4.5 applications ([Amplicon](/dragen/dragen-v4.5/product-guides/dragen-v4.5/dragen-amplicon-pipeline.md), Somatic WGS/Enrichment, Somatic for IDT Custom Panel, [RNA](/dragen/dragen-v4.5/product-guides/dragen-v4.5/dragen-rna-pipeline.md)).

### Configuration

* **Virtual Panels** - Apply virtual gene panels to focus variant review on clinically relevant genes. Virtual panels can be defined based on [disease configuration](/connected-insights/configure/configuration/c-disease-configuration.md) or by entering a custom set of genes.

<div data-with-frame="true"><figure><img src="/files/cuFt4QpHmp5SURJL9rHm" alt="" width="563"><figcaption></figcaption></figure></div>

* **Automatically Report Oncogenicity Prediction** - Oncogenicity prediction can now be configured as a source for [report automation](/connected-insights/configure/configuration/c-automation.md). When enabled, variants with predicted classifications of Oncogenic, Likely Oncogenic, or VUS are eligible for automated biological classification reporting.

<div data-with-frame="true"><figure><img src="/files/sRCbgG6XRuungYW2bkVx" alt="" width="563"><figcaption></figcaption></figure></div>

### Interpretation & Reporting

* **Improved Variant Origin (CHIP and Germline Proxy)** - The Predicted Origin (formerly Origin) column now recognizes [CHIP](/tso500/dragen-tso-500-ctdna-guides/dragen-tso-500-ctdna-v2.6/analysis-methods/tmb.md#clonal-hematopoiesis-ch-variant-identification) (Clonal Hematopoiesis of Indeterminate Potential) variants and [Germline Proxy](https://help.connected.illumina.com/connected-insights/resources-and-references/rar-release-notes/spaces/7XRWgkRPkhoHXVslBqXD/pages/XDUcm9V56hKd9obLJqTa#id-2.-proxi-filter) classifications from supported pipelines. Predicted origin values include Somatic, Germline, and CHIP.

<div data-with-frame="true"><figure><img src="/files/Bsohw8q64NKzt9FAxDCQ" alt="" width="563"><figcaption></figcaption></figure></div>

* **Variant Origin-Specific Assertions** - Assertions now support variant origin context (somatic, germline). Therapeutic, prognostic, and diagnostic evidence from knowledge bases can be filtered and displayed based on variant origin, enabling more precise interpretation and reporting of germline and somatic findings.

<div data-with-frame="true"><figure><img src="/files/E21QFm5wSjtghlR6CYKh" alt="" width="563"><figcaption></figcaption></figure></div>

* **Quick Report Variants** - Report variants directly from the Variants tab without navigating to the Biomarker Details page. Use the Quick Report action to add them to the report using [report automation rules](/connected-insights/configure/configuration/c-automation.md), significantly reducing interpretation time for known variants.

<div data-with-frame="true"><figure><img src="/files/xPwz2QBO5SOzRtdt4hSd" alt="" width="563"><figcaption></figcaption></figure></div>

* **Assertion Update Alert** - When creating a new biological assertion during variant review that changes a variant's highest biological classification to Oncogenic, Likely Oncogenic, Pathogenic, or Likely Pathogenic, an alert notifies you that therapeutic, diagnostic, and prognostic assertions may be affected and suggests refreshing assertions using Update Assertions.

<div data-with-frame="true"><figure><img src="/files/mw70xDw8Yqzj2rZuLnbj" alt="" width="458"><figcaption></figcaption></figure></div>

* **Additional KB Assertions (Deletions)** - OncoKB and CIViC deletion biomarkers are now mapped as copy number variant assertions with copy number decrease consequence, enabling proper matching to CNV deletion events.

<div data-with-frame="true"><figure><img src="/files/0O6WbdwDZpSmxVmeRKxQ" alt="" width="563"><figcaption></figcaption></figure></div>

* **MyKB UX Enhancements** - The assertion side panel is now embedded directly in the page rather than overlaying existing content, improving visibility during interpretation.

<div data-with-frame="true"><figure><img src="/files/r8tACIOhgI6CeJ7ibaIX" alt="" width="563"><figcaption></figcaption></figure></div>

* **Partial Fusion Assertions for Single-Gene RNA Fusions** - Users can now create partial fusion assertions for RNA fusion variants that have only one identified gene, removing the previous requirement for two identified genes.

<div data-with-frame="true"><figure><img src="/files/5A2VXkTlQXBoQXlI8ZuW" alt="" width="563"><figcaption></figcaption></figure></div>

### Visualization

* **Longitudinal View** - Monitor tumor progression over time with a new longitudinal view. Track MRD scores (eVAF), maximum somatic VAF, and individual monitored variant VAFs across related cases. Visualize trends with interactive plots displaying up to 50 cases per subject.

<div data-with-frame="true"><figure><img src="/files/FcMuFarL0K8a808HFyel" alt="" width="563"><figcaption></figcaption></figure></div>

<div data-with-frame="true"><figure><img src="/files/zxyHZVpMZ0iCnQH5CXxF" alt="" width="563"><figcaption></figcaption></figure></div>

* **Circos Plot Enhancements** - Improved Circos plot visualization with fusion labels overlapping key genes, better negative space between chromosomes, legend display, and color improvements.

<div data-with-frame="true"><figure><img src="/files/w5foPLZ4Lr3Q3eGd3HZ9" alt="" width="563"><figcaption></figcaption></figure></div>

* **Base Mismatch Display for Non-MD Tagged BAMs** - Genome browser now displays base mismatches when using BAM files that do not contain MD tags.

<div data-with-frame="true"><figure><img src="/files/bfVrs23OlRqS6oKlnhBM" alt="" width="563"><figcaption></figcaption></figure></div>

### Additional Capabilities

* **Modify Case Display ID** - Users can modify the Case Display ID during review for cases created via manual VCF ingestion.

<div data-with-frame="true"><figure><img src="/files/arw0AnLOMKYRO06gdEqe" alt="" width="563"><figcaption></figcaption></figure></div>

* **Bulk Country Code Entry for Clinical Trials** - When configuring clinical trial [automation](/connected-insights/configure/configuration/c-automation.md), multiple country codes can now be entered as a comma-separated list for faster setup.

<div data-with-frame="true"><figure><img src="/files/J6ad5aPqEFQzN8rDBoaL" alt="" width="563"><figcaption></figcaption></figure></div>

* **Usage Explorer Link** - A link to Usage Explorer is now available in the user profile dropdown menu for administrator users.

<div data-with-frame="true"><figure><img src="/files/H5Jq1AquVO38dQShvHQy" alt="" width="225"><figcaption></figcaption></figure></div>

## Defect Repairs

* 9511: Fixed an issue where changing a subject name to an existing subject caused an error
* 10920: TSO500 RNA analysis and DRAGEN RNA v4.3, v4.4 analysis containing DRAGEN RNA splice variants can now merged with Tumor-Normal DNA analysis successfully
* 10993: Variants with GermlineSatus=Germline\_Proxi are now correctly categorized as Germline in Predicted Origin
* 11009: Default lower spec limit of % Passing Filter QC metrics of TSO500 pipelines should be 55
* 11543: The display order of DNA and RNA samples is now determined in report
* 11558: Mutational signature distribution plot for Double Base Substitution (DBS) now displays in the expected xaxis order
* 11637: Fixed an issue where a “Deletion In Progress” case showed an incorrect status when reloading the case list page
* 11824: Fixed a rare display issue in Actionability filter options when creating or editing a variant filter
* 11853: Fixed an issue that amino acid position may change when scrolling through visualization
* 11930: Fixed default curation level for SV deletion variants to Gene level
* 11934: Gene expression equivocal biomarkers now match both expressionpositive and expressionnegative assertions
* 11961: Fixed an issue changing assertion status to pending approval may fail on gene information assertion
* 11965: Warning bar now correctly appears on the mutational signature page for WES or panel TumorNormal analyses
* 11978: Fixed an issue that the Age field didn't updated after transfer a case to a other subject
* 11993: Fixed an issue when a single VCF file with a upper case file extension VCF used in an merged analysis case
* 12013: Fixed an issue when approve a large report with low coverage region data
* 12040: Gene coverage threshold now correctly applied merging DNA and RNA cases
* 12060: IHC/FISH gene level biomarker is allowed to be added to a case with 0 variant
* 12063: Fixed an issue that intron information was missing for RNA Splice variant in report JSON
* 12099: Fixed an issue that some of OncoKB actionability assertion is missing from biomarker summary table when no biological assertion reported on the same variant
* 12113: Fixed an issue that gene coverage threshold is not applied when re-analysis a case
* 12115: The variant without OMIM value will always be at the bottom of table when users are sorting Variants table using OMIM column
* 12119: Fixed some clinical trials that missing zip code or post code information
* 12152: Fixed VAF calculating in TumorNormal VCFs when the FORMAT field contains “.”
* 12175: Deletion biomarkers in OncoKB and CIViC now match with only variants with Copy Number Decrease consequence
* 12180: Resolved a discrepancy between the oncogenicity prediction shown in the Variants page and the prediction displayed on the variant details screen
* 12201: Users can now modify QC metric thresholds for workgroupspecific pipelines
* 12215: Fixed an issue where the deprecated Sample Metrics filter from earlier releases did not appear in the UI after upgrading a workgroup to v5.4, even though the filter logic was still functioning
* 12296: Fixed an issue that TMB, MSI biomarker were missing in the Merged Analysis when DNA and RNA case was in different analysis
* 12313: Fixed an issue where fewer variants were included in mutational signature analysis for GRCh37 cases.
* 12261: Fixed an issue where the variant detail page failed to load for large variants in rare situations
* 12427: “Created By” filter now works correctly on the case list page
* 12283: Fixed an issue where deleting cases could fail when multiple cases under the same subject were deleted simultaneously
* 12406: Fixed an issue where newly created biological assertions did not appear on the variant detail page without a refresh
* 12573: Fixed a typo in the approval authority in Report Automation Configuration (PDMA PMDA)
* 12691: Fixed an issue where duplicate Tumor VAF columns were displayed in TumorNormal + RNA (threesample) analyses

## Known Issues

* 1298: Read order in the BAM track may change after zooming in the IGV viewer.
* 3723: The software will display two duplicating variants if they were called by two different pipelines, for example, a small variant caller and a structural variant caller.
* 3777: Users will not be able to upload NR transcripts into My Knowledge Base. CKB assertions will not be displayed for NR transcript variants.
* 3934: Reopening an approved report does not trigger notification of assertion update even if there are updated assertions for the case.
* 3943: For DRAGEN RNA pipeline, RNA BAM track in IGV Web is not enabled by default for small variants and needs to be turned on manually.
* 5133: User preferred transcripts for a gene may not be prioritized as expected if user uploads preferred transcripts file with incorrect gene-transcript pairs
* 5491: Coverage graph may not display findings if they use a different transcript rather than the one used to create the graph.
* 5494: In IGV Web, the SV variant track may show only one SV when multiple SVs are present in the same locus.
* 6199: Data upload of analysis results generated by the DRAGEN WGS Somatic v4.2 pipeline fails when the pipeline was run on ICA starting with BAM files. A workaround is to download data locally first. Alternatively, users can manually create a sample sheet and upload it into the analysis output folder in ICA before the analysis is completed. When the analysis is complete, the output will be automatically uploaded into Connected Insights.
* 6200: Variant filtering based on SpliceAI score and gene name may return incorrect results due to use of different transcripts.
* 6584: COSMIC links for some variants lead to non-existing pages due to inconsistencies in content provided by COSMIC.
* 7336: When assertions from multiple knowledge sources are present on different transcripts of a variant, the default transcript may not be the transcript with the highest oncogenic classification.
* 8403: Annotations including CGC, ClinGen, OMIM, 1000 genomes, and custom annotations are not displayed or filterable for SV deletions and CNVs over 10 Mb in size. It can cause these events to be omitted when filtering by annotations. Review of genome view and Circos plots are recommended to identify these larger events (seen as a large deletion arc in the SV track or abnormal coverage in the coverage and CNV track) and also by filtering for SVs and CNVs with length over 10 Mb.
* 10844: Data cannot be sent to IGV desktop when using Connected Insights on Safari.
* 12024: Some benign variants are not automatically marked as reviewed.
* 12017: Some co-occurring assertions for oncogenic variants may display for copy number gains when they are not applicable.
* 12015: NCT06904066 (phase I) is not ingested as since clinical trials are not yet supported for HLA genotypes.
* 11927: Report automation may report clinical trials for Australia when EU is specified.
* 11905: Report automation does not report FDA resistance assertions when FDA is specified.
* 11904: Once a gene threshold has been specified, and the disease is changed for a case ingested in <5.3, only new disease-specific genes will have the specified threshold applied.
* 11900: When report automation is re-run on cases ingested in <5.3, assertions reported may be out-of-sync with assertions displayed.
* 11151: In the transcript modal for RNA fusions, some transcript pairs may be annotated as inframe when at least one of the other transcripts pairs are inframe.
* 10828: When merging a TN DNA case with an RNA case, the DNA BAM may not display in biomarker details.
* 10809: Some non-PASS CNVs are not plotted in the correct color in the whole genome and biomarker details visualization.
* 12415: Deleted KB assertions by the monthly KB update process are not showing in the Variants table or Variant detail page, it blocks report sign off if such assertion was added to draft report before the KB update, because users will not be able to remove them from the report.
* 12580: Unable to download large MyKB contents from the My Knowledge Base UI (API download works correctly).
* 12729: Gene expression biomarker creation is not allowed without specifying a source.
* 12735: HRD column appears empty in the KB table on the variant detail page for BRCA1 and BRCA2.
* 12742: Users should not be allowed to update the selected transcript in a Completed case.
* 12744: RNA BAM track is missing for DNA/RNA merged cases.
* 12745: Multibiomarker selection from the Variants page is not working as expected.1298: Read order in the BAM track may change after zooming in the IGV viewer.
* 3723: The software will display two duplicating variants if they were called by two different pipelines, for example, a small variant caller and a structural variant caller.
* 3777: Users will not be able to upload NR transcripts into My Knowledge Base. CKB assertions will not be displayed for NR transcript variants.
* 3934: Reopening an approved report does not trigger notification of assertion update even if there are updated assertions for the case.
* 3943: For DRAGEN RNA pipeline, RNA BAM track in IGV Web is not enabled by default for small variants and needs to be turned on manually.
* 5133: User preferred transcripts for a gene may not be prioritized as expected if user uploads preferred transcripts file with incorrect gene-transcript pairs
* 5491: Coverage graph may not display findings if they use a different transcript rather than the one used to create the graph.
* 5494: In IGV Web, the SV variant track may show only one SV when multiple SVs are present in the same locus.
* 6199: Data upload of analysis results generated by the DRAGEN WGS Somatic v4.2 pipeline fails when the pipeline was run on ICA starting with BAM files. A workaround is to download data locally first. Alternatively, users can manually create a sample sheet and upload it into the analysis output folder in ICA before the analysis is completed. When the analysis is complete, the output will be automatically uploaded into Connected Insights.
* 6200: Variant filtering based on SpliceAI score and gene name may return incorrect results due to use of different transcripts.
* 6584: COSMIC links for some variants lead to non-existing pages due to inconsistencies in content provided by COSMIC.
* 7336: When assertions from multiple knowledge sources are present on different transcripts of a variant, the default transcript may not be the transcript with the highest oncogenic classification.
* 8403: Annotations including CGC, ClinGen, OMIM, 1000 genomes, and custom annotations are not displayed or filterable for SV deletions and CNVs over 10 Mb in size. It can cause these events to be omitted when filtering by annotations. Review of genome view and Circos plots are recommended to identify these larger events (seen as a large deletion arc in the SV track or abnormal coverage in the coverage and CNV track) and also by filtering for SVs and CNVs with length over 10 Mb.
* 10844: Data cannot be sent to IGV desktop when using Connected Insights on Safari.
* 12024: Some benign variants are not automatically marked as reviewed.
* 12017: Some co-occurring assertions for oncogenic variants may display for copy number gains when they are not applicable.
* 12015: NCT06904066 (phase I) is not ingested as since clinical trials are not yet supported for HLA genotypes.
* 11927: Report automation may report clinical trials for Australia when EU is specified.
* 11905: Report automation does not report FDA resistance assertions when FDA is specified.
* 11904: Once a gene threshold has been specified, and the disease is changed for a case ingested in <5.3, only new disease-specific genes will have the specified threshold applied.
* 11900: When report automation is re-run on cases ingested in <5.3, assertions reported may be out-of-sync with assertions displayed.
* 11151: In the transcript modal for RNA fusions, some transcript pairs may be annotated as inframe when at least one of the other transcripts pairs are inframe.
* 10828: When merging a TN DNA case with an RNA case, the DNA BAM may not display in biomarker details.
* 10809: Some non-PASS CNVs are not plotted in the correct color in the whole genome and biomarker details visualization.
* 12415: Deleted KB assertions by the monthly KB update process are not showing in the Variants table or Variant detail page, it blocks report sign off if such assertion was added to draft report before the KB update, because users will not be able to remove them from the report.
* 12580: Unable to download large MyKB contents from the My Knowledge Base UI (API download works correctly).
* 12729: Gene expression biomarker creation is not allowed without specifying a source.
* 12735: HRD column appears empty in the KB table on the variant detail page for BRCA1 and BRCA2.
* 12742: Users should not be allowed to update the selected transcript in a Completed case.
* 12744: RNA BAM track is missing for DNA/RNA merged cases.
* 12745: Multibiomarker selection from the Variants page is not working as expected.

## **Revision History**

<table><thead><tr><th width="100">Version</th><th>Description of Change</th></tr></thead><tbody><tr><td>00</td><td>Initial Release</td></tr></tbody></table>


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