Curate Variant page

The Curate Variant page presents the most clinically relevant variant information.

The Curate Variant page is comprised of:

Top bar

that lists:

1. Gene symbol. When clicked, the software directs you to Curate genes

2. HGVS descriptions for genomic DNA, coding DNA, and protein-level changes

3. Variant effect

4. Pathogenicity. Note: you can change Pathogenicity by selecting a different option from the dropdown menu

Interpretation card

that features:

1. The Curated tab intended to be used for your curated variant interpretation. This text can be reused in the Variant Interpretation notes within a case

2. The Note tab for your draft notes on the variant

Note: to edit your notes, select the tab (Curated or Note), and press the Edit button. Edit the text and apply the formatting. Don't forget to click Save!

Gene's related diseases card

that includes:

1. The number of gene-associated diseases as reported in OMIM, ORPHANET, CGD, ClinVar, and academic papers included in the Emedgene knowledge graph

2. The currently selected condition

3. Links to data sources

4. Inheritance mode icons where available

5. A Change button that opens the disease selection menu

Variant information card

that highlights:

1. The Type of variant

2. Main Effect relevant to the selected transcript

3. Gene symbol

4. HGVS format for coding and protein levels changes

Note: You may select a different reference transcript from the dropdown menu.

Note: To copy the HGVS descriptions in the clipboard, click on the copy icon on the right.

ACMG Classification card

The ACMG Classification system in Emedgene supports a streamlined and flexible workflow across Analyze and Curate, allowing users to apply, manage, and reuse ACMG evaluations more effectively. Whether you're annotating a new variant or updating existing records, the tools available help maintain traceable and consistent variant interpretations.

Storing and Managing ACMG Classifications in Curate

You can store ACMG classification tags within Curate, enabling automated or manual application of ACMG logic to variants. This supports both new Curate entries and updates to existing ones.

How Stored ACMG Tags Work

• Stored ACMG tags in Curate include classification logic, tag strength, tag-specific notes, and scores

• These tags can be edited by users with the appropriate role and viewed (but not changed) by other users

• Whenever tags are added or modified, the system automatically recalculates the overall pathogenicity classification and score

• All changes to ACMG tags—including activation/inactivation, tag strength adjustments, and classification updates—are logged under Activities > Curate ACMG

_{Note: Changes to ACMG notes are not recorded in the activity log.}

How Stored Classifications Are Applied in Analyze

When analyzing a case that contains variants with ACMG tags stored in Curate:

• The existing ACMG classification is automatically applied to those variants

• This includes consideration of tag status (positive/negative), questions answered (yes/no), tag strength, and any associated notes.

• These classifications are clearly marked as coming from Curate

Updating ACMG Data from Analyze

While reviewing a variant in Analyze, you have multiple options to interact with Curate:

1. Curate Button Actions

Depending on whether the variant exists in Curate and your user permissions, the Curate button offers:

• Add to Curate: For new variants not yet in Curate

• Update in Curate: For existing variants. Updates include:

  • Pathogenicity classification

  • Variant interpretation

  • Associated gene-disease connection (unless custom)

  • Selected transcript (unless custom)

  • ACMG classification details (tags, score, strength, and notes)

• Open in Curate: To view the stored Curate entry (available in previous versions as well).

This functionality ensures variant data stays synchronized across Curate and Analyze without manual duplication.

1. Curate ACMG - Schema version warnings

When working in Curate, Emedgene keeps track of the ACMG schema version used for each curated SNV. If the variant was curated using an older schema than the one currently active in Analyze, you’ll see a warning in the ACMG section of the variant.

Using an outdated schema may mean your classification is missing updated logic, revised strength definitions, or newly excluded tags.

1. Enhanced Activity Logging

To improve traceability:

• Any update to a Curate entry via Analyze will now be reflected in the Activity Log, capturing the full history of changes

• Changes related to ACMG classification are grouped under a dedicated Curate ACMG category

Use Case Example

When evaluating a variant in Analyze:

1. Apply ACMG tags either manually or via auto-classification

2. Use the Update in Curate button to sync this evaluation into your Curate database

3. If the same variant is later reviewed in another case, the stored classification is automatically retrieved—saving time and maintaining consistency

This ACMG classification integration helps streamline your interpretation workflow, supports traceability, and ensures that your variant evaluations are consistently reused and refined across the platform.

Related Cases card

that shows, for every case within your organization containing the tagged variant of interest*:

1. Case name and genomic reference

2. CNVs: Variant Details (genomic coordinates and size)

3. CNVs: dynamic annotation overlap percentage filter

4. CNVs: Annotation Overlap

5. Previously assigned Pathogenicity

6. Case creation Date

7. Previously assigned variant Tag

8. Variant Inheritance

9. Link to the case

*For CNVs, all overlapping variants are displayed in the table. The minimal annotation overlap percentage filter is initially set to 70%, but it can be adjusted manually (1-100%).

Network Summary card

that shows, for each occurrence of the variant in each Curate database maintained by collaborators within your Network

1. Collaborator

2. CNVs: Variant Details (genomic coordinates and size)

3. CNVs: dynamic annotation overlap percentage filter

4. CNVs: Annotation Overlap

5. Pathogenicity

6. Case creation Date

7. SNVs: Transcript

8. Gene Related Disease

9. Variant Interpretation in the dropdown

*For CNVs, all overlapping variants are displayed in the table. The minimal annotation overlap percentage filter is initially set to 70%, but it can be adjusted manually (1-100%).

Variants displayed in your Curate Variants table, which only have a Network Summary tab on the Variant page, are previewed from your collaborator(s)' Curate database(s) and are not part of your Curate database. To add such a variant to your Curate, click on Import button. Once added, you're free to edit Pathogenicity, Interpretation notes, Gene's Related Diseases, and Variant Transcript to your preference.

Activities panel

The Activities panel records a history of user activities on the Curate Variant page. Click on the Activities button to open it.

Maximize button

The arrow icon on the top left of the Curate Variant page is a button that switches the view mode between:

1. Curate Variant table is hidden, while Curate Variant page is maximized

2. Curate Variant table is shown, while Curate Variant page is reduced