Recording Interpretation

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 the tracking of the analysis and interpretation of the case and the variants identified. This can be performed on the variant grid and in the interpretation section on the variant details page. These allow for variants to be commented on, classified and a contribution to phenotype and transcript 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 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 variant grid or the Classification panel in the variant details page.

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

Add to reportExclusionVariant commentTranscript selectionContribution to phenotypeClassification

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 all fields in the classification drawer have been completed. This is because the information is required in order to pass the variant to CVA. 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.

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 Other reviewed variants table by default. Any attempt to add an excluded variant to the report will result in an error message.

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, 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.

Exclusion comments

Exclusion comments can be edited or removed by any user, by opening the menu next to the comment and clicking Edit or Delete. This allows for easy removal in the case of any accidentally included patient identifiable information (PID). When an exclusion comment is edited, the username and timestamp associated with the comment will update to that of the current user and the current time, and the comment will become the most recent comment (therefore the comment that is displayed at the top of the classification panel).

When an exclusion comment is deleted, the comment text will be replaced by Removed, and the comment displayed in the classification panel will either be cleared if there was no previous version of the comment, or it will revert to the previous version of the comment.

Variant comment

Comments can be added using the Variant comment box in the Classification pane. Clicking Cancel will prevent the comment from being saved, and this can be checked in the History pane. See the history page for details on editing comments. There is a maximum limit of 1024 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 any user, by opening the menu next to the comment and clicking Edit or Delete. This allows for easy removal in the case of any accidentally included patient identifiable information (PID).

When a variant comment is edited, the username and timestamp associated with the comment will update to that of the current user and the current time, and the comment will become the most recent comment (therefore the comment that is displayed at the top of the classification panel).

When a variant comment is deleted, the comment text will be replaced by Removed, and the comment displayed in the classification panel will either be cleared if there was no previous version of the comment, or it will revert to the previous version of the comment.

Transcript selection

If the variant has any associated gene(/s), a transcript selection can also be added alongside the classification. If it does not then this drop down will not be displayed for the variant.

Transcripts available in the drop down are grouped by gene, with a flag displayed next to the transcript to indicate whether it has the most severe consequence for the gene (S), and whether it is a Mane Select (M) or Mane Plus Clinical (M+) transcript. A transcript could have no flags if it does not produce the most severe consequence for the gene, it could have only one of S, M or M+, or it could have a combination of multiple of these. Currently the transcripts in the drop down are not ordered in any specific priority.

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

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.

Classification

The classification is based on the ACGS/ACMG system and classifies a variant as one of Benign, Likely benign, Uncertain significance, Likely pathogenic 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.

Abbreviations

Abbreviation	Definition
ACGS	Association for Clinical Genomic Science
ACMG	American College of Medical Genetics and Genomics
CDS	Coding DNA Sequence
CNV	Copy Number Variant
CVA	Clinical Variant Ark
New IB	New Interpretation Browser
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
IP	Interpretation Portal
NGIS	National Genomics Informatics System
PID	Patient Identifiable Data
QC	Quality Control
SO	Sequence Ontology
SNV	Single Nucleotide Variant
SV	Structural Variant
TOMS	Test Order Management Service
UAT	User Acceptance Testing
VCF	Variant Call Format File
WGS	Whole Genome Sequencing