Version 13.12.0 of VarSome was released on 23 October 2025.

This scheduled maintenance update focused on ensuring system stability and preparing the platform for upcoming improvements.

note: ClinVar's most recent data release introduced major structural changes. To ensure data consistency and accurate integration, this update is under internal validation. ClinVar's monthly updates will resume after this validation process concludes.

Version 13.12.0 of VarSome Clinical will be released on 30 October 2025.

Summary of Key New Features

• CNV filtering for Delly whole-genome analyses
• TMB and MSI biomarker visualization
• Support for Twist UMI-based assays
• PAR masking for hg38 reference genome
• Editable group gene lists
• Repeat expansion annotation from PacBio VCFs
• Somatic PVS1 rule fix
• ClinVar update temporarily on hold

New Features

CNV Delly Filtering

Users can now apply a shortcut filter to CNVs generated from whole-genome analysis with Delly. This new filter automatically removes low-confidence CNVs and those larger than 100 Kb, which are typically false positives or inherently pathogenic due to size.

By allowing users to toggle between filtered and complete result sets directly from the results table, this update reduces noise and false positives, improving confidence in CNV interpretation, and streamlines variant review by focusing on high-quality CNV calls.

This enhancement applies to WGS CNV analyses from FASTQ files.

Fig. 1 - Shortcut filter

TMB and MSI Visualization

A new “Sample Biomarkers” button appears below the variant table in somatic WES and Agilent CGP Panel analyses. From this section, users can view TMB and MSI evidence and access therapeutically relevant information via JAX CKB, OncoKB™, CIVIC, FDA-approved drugs, and AACT Clinical Trials.

This integration allows users to explore biomarker-specific treatment evidence and make faster, evidence-based decisions by reducing the need to cross-reference multiple sources.

Fig. 2 - Sample Biomarkers button

Fig. 3 - View the TMB evidence

Fig. 4 - View the MSI evidence

Fig. 5 - View the OncoKB™ information 

Support for Twist UMI-based Assays

VarSome Clinical now supports Twist Bioscience UMI processing, following official Twist guidelines.
The pipeline extracts dual UMIs, tags them during preprocessing, and collapses reads into error-corrected consensus BAMs, ensuring enhanced variant-calling accuracy, particularly for low-frequency variants and liquid biopsy applications.

This feature broadens compatibility with Twist’s UMI-based panels, ensuring a consistent analytical experience across assays.

Read our full application note with Twist Bioscience here.

PAR Masking for hg38 Reference Genome

To improve read alignment and variant calling in sex chromosomes, the pseudoautosomal regions (PARs) on chromosome Y of hg38 are now masked (replaced with Ns).

This correction aligns hg38 with best practices already applied in hg19 and improves variant calling accuracy in the sex chromosomes by preventing ambiguous read alignments between X and Y.

Minor Fixes and Additions

• Editable Group Gene Lists: Users can now edit gene lists created within their group and view who created and last modified each list. 
• Repeat Expansion Annotation from PacBio VCFs: Repeat expansion VCFs generated by PacBio are now supported for annotation. Users can evaluate repeat pathogenicity using the integrated gnomAD STR dataset, similar to existing support for Oxford Nanopore Technologies and DRAGEN pipelines. This ensures full platform-agnostic coverage of repeat expansion data across major sequencing technologies.
• Somatic PVS1 Rule Fix: A minor issue affecting PVS1 rule application in somatic mode for VarSome.com and API users has been resolved. Variants in somatic mode now correctly apply the PVS1 rule in all cases.
• ClinVar Update Temporarily on Hold: ClinVar’s most recent data release introduced major structural changes. To ensure data consistency and accurate integration, this update is under internal validation. ClinVar’s monthly updates will resume after this validation process concludes.

Support

We hope you find these improvements helpful. We would love to hear any feedback and suggestions you may have. Support is available as usual from support@varsome.com.

The VarSome Team.