Recording interpretation (STRs)

Disclaimer

The clinical interpretation of referrals and variants should follow your local best practice guidelines.

There are a number of features designed to aid in case and variant interpretation, and tracking those interpretations. STR interpretation can be performed on the variant grid, using the classification drawer. When the classify button is clicked, the row in the grid for the corresponding variant is highlighted in blue, and the variant coordinates are indicated at the top of the classification drawer that opens. The drawer provides the ability for variants to be commented on, classified and a contribution to phenotype and validation requirement / outcome selected. A history of any comments and classification can be seen in the History panel below the classification panel, along with information on who provided the interpretation and when.

Any variant with an interpretation history, which has not been added to the report, will be visible by default in the Other reviewed variants table on the reporting page.

Classification and Exclusion

A variant can be classified or excluded using the Classification drawer on the STR grid.

All fields and buttons are disabled when the case is closed.

Variant commentExclusionContribution to phenotypeValidationClassifyAdd to report

Variant comment

Comments can be added using the Variant comment box in the Classification pane. Multiple comments can be added to the same variant, and the comment box remains visible after each comment is saved, allowing additional comments to be added. Comments are displayed beneath the comment box, with the most recent comment at the top.

By default, the two most recent comments are displayed. Where more than two comments have been added, select Show older comments to view all previous comments. Select Hide older comments to return to the default view.

Clicking Cancel will prevent a comment from being saved. There is a maximum limit of 10,000 characters for comments. If you enter a URL, this will be recognised and loaded as a clickable hyperlink when saving the comment.

Comments can be edited or removed by the user who originally added them, by opening the menu next to their comment and selecting Edit or Remove. Users cannot edit or remove comments added by other users.

When a comment is edited, the updated text is displayed in its original position, retaining the original username and timestamp. An Edited label is displayed next to the comment to indicate that it has been modified.

When a comment is removed, it is no longer displayed in the Variant comment section.

All comments and subsequent edits or removals are recorded in the History panel, including the username, timestamp and comment content. Editing or removing a comment creates a new history entry while preserving the original record for audit-trail purposes. The History panel is read-only. See the history page for further details.

Comments on excluded variants

The Variant comment section remains available when a variant is excluded, allowing users to view existing comments and add new comments without changing the variant's exclusion status.

When a variant is excluded, the Variant comment section is displayed beneath Reasons for excluding in the Classification pane. The same functionality for adding, viewing, editing and removing comments applies to both included and excluded variants.

Variant comments are optional when excluding a variant.

Exclusion

Excluded variants are variants that have been determined to not require any further interpretation or classification for a specific reason, such as being an artefact or being too common.

A variant can be excluded by clicking the Exclude variant button in the Classification pane. This will update the classification at the top of the card to Excluded, hide the fields for classifying the variant, and reveal two new fields, to select one or multiple reasons for excluding the variant, and add an associated comment to record rationale (both optional fields). The Reasons for excluding selection options are: Incompatible phenotype, No relevant disease association, Inherited from unaffected parent, No higher than VUS, Non-coding region, Artefact, Common, and Other. There is a maximum limit of 10,000 characters for comments. Selections can be removed by deselecting the selected check-box(es).

To unexclude the variant after exclusion, uncheck the checked Exclude variant box. This will set the classification drawer back to the default view.

Contribution to phenotype

A contribution to phenotype can also be added alongside the classification. The options provided are Full, Partial, None and Unknown.

Selections can be reset using the drop down menu and selecting Reset contribution to phenotype, and the drop down will then display Select.

Validation

This drop down allows the user to record any validation requirements or validation results for the STR. The options provided are Confirmation required, No confirmation required, Confirmed, and Artefact.

Selections can be reset using the drop down menu and selecting Reset validation, and the drop down will then display Select.

Classification

The user can classify a variant as Benign, Uncertain significance and Pathogenic.

The classification can be made by selecting the classification from a drop down menu and clicking Classify to save. This will also save a record in the variant history with the classification, name of person who classified, and the time and date. Classifications cannot be edited but new classifications can be made by reselecting from the drop down menu. This will change the overall classification but the prior classification(s) will remain in the variant history.

Selections can be reset using the drop down menu and selecting Reset classification, and the drop down will then display Select, and the classification at the top of the card will reset to None Selected.

Add to report

Variants can be added to the Variants to report table in the reporting page by clicking the Add to report button at the top of the classification drawer. Clicking the button again will then remove the variant from the report.

Pathogenic and Likely Pathogenic classifications

Variants with Pathogenic or Likely pathogenic classification selected can only be added to the report if the Variant comment and Contribution to phenotype fields have been completed. Any attempt to add the variant to the report by clicking the Add to report button without completing all fields will trigger an error message to indicate that those fields are required. Once those fields have been filled in, then the error messages will disappear and clicking the Add to report button will now successfully add the variant to the Variants to report table. The Add to report button will be replaced by a Remove from report button which can be used to remove the variant from the Variants to report table.

If the selection for any field is cleared after it has been added to the Variants to report table, then the variant will be automatically removed from the table and be moved into the Other reviewed variants table.

Unlike classified SNVs, classified STRs are not passed to CVA.

All other classifications

Variants with any other classification types or without a classification selected can be added to the report by clicking the Add to report button, with no mandatory fields required.

Excluded variants

Excluded variants are added to the Excluded variants table by default.

Abbreviations

Abbreviation	Definition
ACGS	Association for Clinical Genomic Science
ACMG	American College of Medical Genetics and Genomics
CDS	Coding DNA Sequence
CIP-API	Genomics England Clinical Interpretation API
CNV	Copy Number Variant
CVA	Clinical Variant Ark
EQ	Exit Questionnaire
RDDSS	Rare Disease Decision Support System
GEL	Genomics England
GMS	Genomic Medicine Service
GLH	Genomic Laboratory Hub
HGVS	Human Genome Variation Society
HTML	Hyper Text Markup Language
HSCN	Health and Social Care Network (N3)
IGV	Integrative Genomics Viewer
IB	Interpretation Browser
IP	Interpretation Portal
NGIS	National Genomics Informatics System
PID	Patient Identifiable Data
QC	Quality Control
SoF	Summary of Findings
SO	Sequence Ontology
SNV	Single Nucleotide Variant
SV	Structural Variant
TOMS	Test Order Management System
UAT	User Acceptance Testing
VCF	Variant Call Format File
VILs	Variant Interpretation Logs
WGS	Whole Genome Sequencing