Evaluation Summary

The first section provides a summary of the variant classification (auto-calculated and modified), disease association, mode of inheritance, and any associated specification document.

Following the summary information, there are three fields available to edit:

A. Modify Classification: pull-down which allows curator to select the pathogenicity

B. Reason(s) for change: free text box for curators to explain why they selected an alternative pathogenicity to the one calculated

C. Evidence Summary: free text box for curators to summarize their evidence and provide a rationale for the clinical significance

Criteria Tables

At the bottom of the Summary page, all of the ACMG criteria are split into three separate tables according their evaluation status. These tables are not editable in Summary View. To make changes, you must return to Interpretation Mode.

Criteria meeting an evaluation strength

Criteria evaluated as 'Not met'

Criteria 'Not yet evaluated'

Each table summarizes the evaluations made for each criterion into the following fields:

• B/P: Red icon indicates pathogenic; purple icon indicates benign. “Met” criteria have ticks in a circle, “Not met” have crosses in a circle, and “Not evaluated” criteria have an empty circle.

• Criteria: Listed using their ACMG criteria codes; color indicates pathogenicity on a scale from ‘purple’ benign to ‘red’ pathogenic.

• Criteria Descriptions: Brief descriptions of the ACMG criteria.

• Modified: For "met" criteria, ‘yes’ or ‘no’ indicates whether the criterion has a modification. "Not met" and "Not evaluated" criteria will display N/A.

• Status: Criteria are shown as “Met”, “Not Met” and “Not evaluated”. Additionally, “Met” indicates any modifications: _Strong, _Moderate, _Supporting, _Very strong, _Stand-alone.

• Explanation: Displays criterion-level explanation provided by the curator.

To select an alternative classification:

1. Select the appropriate option from the Modify Classification pull-down.

2. Provide a reason for the change in the free text box.

3. Click

After saving the modified classification and reason for change, the Evaluation Summary will update.

Once you have evaluated all the evidence to your satisfaction, click to view a Summary of all your evaluations:

The Summary View has two sections.

1. Evaluation Summary

2. Three tables displaying ACMG criteria, divided according to evaluation status

When to Save a Summary

You will need to Save the Evaluation Summary:

1. If you want to Save any any edits made to the "Modify Classification", "Explain reason(s) for change", and/or "Evidence Summary" fields, OR

2. If you want the option of making a Provisional Interpretation based on the current evidence/evaluations.

In Progress Status

The first time an Evaluation Summary is saved the status of the Interpretation will change to "In Progress". The Interpretation will remain "In Progress" until a summary is saved as Provisional.

Saving New Summaries

Every time the Save button is clicked in the Evaluation Summary, any previous summary is overwritten and the ‘Interpretation Last Edited’ is appended with a "New Saved Summary" label.

What do the different record statuses mean?

In Progress

• In progress is used for any record NOT in a provisional or approved status. It denotes records that are still being worked on and have not yet had a snapshot saved.

Provisional

• Provisional status is used by curators to mark their Interpretation as complete after saving an Evaluation Summary

• Provisional Interpretations created by Affiliations are considered ready for their expert review

Approved

• Approved status is used after Provisional Classification has passed the review and approval process

• The option to Save as Approved appears after saving an Interpretation as Provisional

• Some Affiliations may require final ratification by a designated Approver, in which case the curator must select the name of the Approver from a pre-populated pull-down

• Users working independently can choose to Approve their Interpretations whenever they wish.

Approval Process Workflow

How to Save as Provisional

Upon saving a classification and/or changing/updating the Evidence Summary text the ‘Save’ button will change to an ‘Edit’ button and a “Save Interpretation as Provisional” section will appear.

B. ClinGen Affiliation: If the curator is curating as part of an Affiliation, this field will display that affiliation. If not curating as part of an Affiliation, it will display "--"

C. Provisional Classification entered by: Field will auto-populate with curator's name after clicking "Preview Provisional"

D. Date Reviewed: Field will auto-populate with current date. Curator may also enter a date manually (MM/DD/YYYY) or select from the calendar. Note: Dates in the future should never be selected!

E. Additional Comments: Optional field for capturing additional notes about the review process

Provisional Preview

In preview mode, the curator has three options:

1. Cancel Provisional Returns to prior view and cancels the Saving as Provisional process. Any additional comments will be deleted, and the Date reviewed returns to the current date.

2. Edit Returns to prior view and allows the curator to go back and correct any errors. Additional comments and date changes are saved.

3. Submit Provisional Permanently saves the current Interpretation as a Provisional Interpretation

Current New Provisional

Upon Saving a new Provisional Interpretation it will appear at the top of the "Saved Provisional and Approved Interpretation(s)". The current Saved Provisional Interpretation will always be marked with a green flag.

New Saved Provisional Interpretations

Every time a curator updates an Interpretation (e.g. new evidence, new evaluations, etc.) they can choose to Save the updates by clicking the Save button in the Evaluation Summary. They will then be invited to Save that new Interpretation as Provisional.

Archiving Provisional Interpretations

Upon Saving a New Provisional Interpretation then that will now be the new current Saved Provisional and will appear at the top of the "Saved Provisional and Approved Interpretation(s)" panel and be marked with a green flag. The previous current saved Provisional Interpretation will now become archived, and its green flag will be replaced with a grey archive box.

How to View Summaries

Upon saving all Provisional and Approved Interpretations a snapshot of their Evaluation Summary is also saved. A Summary is viewable for each Interpretation from the "Saved Provisional and Approved Interpretation(s)" on the Evaluation Summary page by clicking on the "View Provisional Summary" and "View Approved Summary" buttons. For archived Interpretations these buttons appear gray but they are still active linkouts to the Summaries.

Summaries

A Summary snapshot will contain a Summary table at the top with information about the Interpretation, followed below by the Evidence Summary, and finally the criteria tables underneath.

Printing Summaries

Recommended print settings:

• Layout: Landscape

• Scale: 50%

• Margins: Minimum

• Background graphics selected

You can also use your Print dialogue box to save your Interpretation as a PDF.

How to start Approval Process

After a Provisional Interpretation is Saved, an orange "Approve Interpretation" panel will appear above the "Saved Provisional and Approved Interpretation(s)". This panel enables a curator to begin the process of Approving the current Saved Provisional Interpretation.

If a curator navigates away from the Evaluation Summary page, when they return they will still have the option of starting the Approval process for the current Saved Provisional Interpretation. To do so they should simply click on the orange "Approve this Provisional Interpretation" button found within the current Saved Provisional Interpretation.

Saving as Approved

All Approvals are processed via the orange Approve Interpretation panel

A. ClinGen Affiliation: If the curator is curating as part of an Affiliation this field will autofill, otherwise it will be blank.

B. Entered by: After clicking "preview approval" this field will auto-fill with the name of the curator.

C. Select Approver: Approver(s) identified by the Affiliation will be listed in the pull-down. An approver must be selected to proceed.

D. Final Approval Date: By default, this populates with the current date. A curator can optionally enter a PAST date from the calendar. Note: Dates in the future should never be selected!

E. Approver Comments: Optional field for capturing additional notes about the approval process.

F. Preview Approval: Click to initiate the process to Approve the Interpretation.

Approval Preview

In Preview mode the curator has three options:

1. Cancel Approval - this cancels the Saving as Approved process

2. Edit - this allows the curator to go back and correct any errors (e.g. in the Additional Comments)

3. Submit Approval - this will permanently Save the current Interpretation as an Approved Interpretation

New Saved Approved Interpretation

After clicking Submit Approval, the new Approved Interpretation will appear at the top of the "Saved Provisional and Approved Interpretation(s)". The current Saved Approved Interpretation will always be marked with a green flag. Older Approved Interpretations are noted by a grey archive box.

The curator will also be presented with publishing options (see Publishing from the VCI)