Recording Interpretation¶
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.
Classification and Exclusion¶
A variant can be classified or excluded using the 'Classification' column on the variant grid or the 'Classification' panel in the variant details.
A variant can be excluded by checking the 'Exclude variant' box in the 'Classification' pane. This will update the classification at the top of the card to 'Excluded', and hide the fields for classifying the variant. A new drop-down option will appear upon checking this box, to add a "Reason for excluding variant" if required (this is optional). The options provided are 'Incompatible phenotype', 'No relevant disease association', 'No higher than VUS', 'Artefact', 'Common', and 'Other'. When 'Other' is selected, then "Add comment" can be clicked to save a comment detailing the rationale. There is a maximum limit of 10,000 characters for comments. Selections can be reset using the drop down menu and selecting 'Reset reason for excluding variant', and the drop down will then display 'Select'.
To unexclude the variant after exclusion, uncheck the 'Exclude variant' box. This will set the classification drawer back to the default view.
The classification is based on the 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'.
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 predected 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 predicted 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'.
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'.
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 History section below 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.
History¶
Making selections or adding comments in the classification pane will also save a record in the 'History' pane on the variant details page to provide a record of the selections made. This will include the name of the person who made the selection, the date, the time, the information type recorded (e.g. 'Transcript', or 'Classification'), and the input provided. This input could be a drop-down selection, comment added, or selection of the 'Exclude variant' box. If a comment is entered but the cancel button is clicked, the comment will not be saved in the history.
History items cannot be edited, with the exception of comment history items. These can be edited solely by the user that made the inital comment, by clicking the pencil icon alongside the comment made. This allows for easy removal in the case of any accidentally included patient identifiable information (PID).
All other existing selections can be updated using the respective drop down menu. This will record the updated selection at the top of the history card, and retain any prior selections in the variant history for audit trail purposes.
