Evidence tab

The Evidence Tab provides tools to review, document, and classify variants efficiently. It combines manual and automated features to ensure accurate pathogenicity assessment, interpretation notes, and evidence visualization.

Users can import past interpretations, apply ACMG classification wizards, and generate evidence graphs—all within one workspace. Access is available only for tagged variants, ensuring that evidence review is focused and traceable.

1. Pathogenicity selection

A dropdown menu lets you assign the variant’s pathogenicity manually:

• Pathogenic (P)

• Likely Pathogenic (LP)

• Variant of Uncertain Significance (VUS)

• Likely Benign (LB)

• Benign (B)

If the variant already exists in Curate, its previously assigned classification will display alongside a Curate logo, ensuring consistency across analyses.

Any updates you make here are reflected in both the case summary and reports.

2. Variant Interpretation notes

The Interpretation Notes field contains a draft explanation of the variant, pre-populated with details from the AI Shortlist algorithm.

Editing is supported via the Edit Text link. In edit mode, the Paste icon becomes available, letting you quickly add standardized content.

You can expand notes using the dropdown options:

1. Import data from Curate:

   1. Gene - Import interpretation and gene notes linked to the gene from Curate Genes.

   2. Variant - Import interpretation and variant notes linked to the specific variant from Curate Variants.

   You get:

   • Direct access to the interpretation of the main gene linked to the variant, pulled from Curate.

   • If your variant touches multiple genes, you’ll see all available interpretations from Curate.

   Useful to:

   • Give immediate biological and clinical context to your variant review.

   • Save you from searching for the gene page in Curate.

   You can use it:

   • During review: Use the Notes and Gene Interpretation sections to check your prior conclusions before making new calls.

   • For consistency: Copy relevant reasoning forward into new cases where the same variant appears.

   • For efficiency: Import all notes and interpretations from Curate in one click, rather than digging through old cases.

   Imported notes now include links to supporting evidence and AI phenotype matching scores for easier cross-reference.

2. Choose from related cases - Retrieve summary notes if the same variant has been classified in other cases within your organization. For multi-gene variants like CNVs, each gene’s interpretation and notes are grouped under its name. This is especially useful when you want to:

   • Quickly recall what you concluded in past cases

   • Avoid repeating literature searches you’ve already done

   • Spot consistency (or inconsistency) in your past reasoning

3. Choose from template - Use a predefined variant interpretation template to standardize text.

Tips:

1. Import wisely

• You can pull in content from other cases in your workgroup or from Curate itself

• Imported content is added to the end of your current notes — not replaced — so check for duplication before importing multiple times

1. Keep it clean

• Avoid importing everything blindly — especially in multi-gene variants where unrelated gene notes may appear

• Trim irrelevant content so your notes stay focused and easy to read

1. Update as you go

• If you add new interpretations or notes in Analyze, push them to Curate so future cases benefit from your work

• This keeps both platforms aligned

1. Check permissions

• Only users with the edit evidence text role can edit notes or interpretations here

• If you can’t edit, you can still view past content

1. Use the activity log

• Every change you make is tracked at the variant level and in the case activity stream — useful for audit trails and collaborative work

Warnings:

• Multi-gene caution: For CNVs and other multi-gene variants, importing will bring in all affected genes’ notes and interpretations. Review carefully before saving.

• Outdated content: Notes pulled from old cases might not reflect current guidelines or the latest evidence — verify before reporting.

• Clutter risk: Because imports are appended, importing repeatedly without cleaning up can make your notes section messy and harder to scan.

• Reporting impact: Any interpretation you keep here can make it into your final report — check accuracy before exporting.

3. A See evidence button

A See Evidence button appears beneath the Evidence box.

• This links directly to the Evidence Page, where you can view a graphical breakdown of supporting and conflicting evidence.

• You can also regenerate the Evidence Graph if new information (e.g., phenotype match, curated disease selection) is added.

Warning: After editing the Evidence Graph, phenotypic match strength indicators may disappear from the sidebar and variant page. Always review before finalizing.

4) ACMG SNV Classification wizard

The ACMG SNV Classification wizard:

• Automates classification for sequence variants.

• 26 of 28 ACMG criteria are pre-calculated using Emedgene’s algorithms.

• 2 criteria require manual confirmation (BS2 and PS4).

• A points-based ACMG scoring system is applied in addition to rule-based tagging, aligning with updated ACMG/AMP recommendations.

ACMG CNV Classification wizard

The ACMG CNV Classification wizard:

• Automates classification of copy number variants (CNVs).

• Integrates CNV-specific parameters such as Copy Number, CNV Quality Score, and Size.

• CNV tags are largely automated, but users can review and override assignments as needed.

5) Sanger Confirmation toggle button

• A simple toggle button lets you mark whether the variant:

  • Should be submitted for Sanger validation, or

  • Has already been confirmed by Sanger sequencing.

• This information is stored in the case record and displayed in reports.

Note: Keep in mind that the Evidence tab is active only for variants that have been automatically or manually tagged. To enable the Evidence tab, you need to assign any tag to the variant under consideration.

Tips:

• Use the Curate imports to avoid duplicating work—gene and variant interpretations already validated by your team can be reused.

• Always check phenotype alignment (PP4): if the disease context changes, regenerate the Evidence Graph.

• When using ACMG Wizards, review tags flagged as “manual check”.

• Leverage templates to standardize interpretations across your team, reducing variability in reporting.

Warnings:

• Changing the disease in the Evidence Graph will not automatically change inheritance mode—update this manually to avoid classification errors.

• If you edit the Evidence Graph, phenotypic match strength indicators may disappear from the sidebar and main page. Double-check before finalizing your report.

• Custom disease names (if created for reporting) will only be stored within the case—they will not be added as new gene-disease connections in Curate.