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Overview

Each case in the ValidSpliceMut database is classified as aberrant, likely aberrant, or allele-specific alternative splicing based on a series of evidence types. Steps taken to classify cases are presented in the flowchart below. After a classification has been determined for all cases containing the specified variant in ValidSpliceMut (regardless of tumour type), the most common classification - labelled "Consensus molecular phenotype" - is shown at the top of the results page. Adjacent to the consensus molecular phenotype, the number of cases assigned the most common classification is displayed alongside the total number of cases. Multiple classifications are listed if multiple classifications are equally common.

Classification Evidence Bar

Although cases are classified according to three distinct classifications, there are of course many combinations of evidence types which can lead to a classification (as depicted in the flowchart above). During case classification, all evidence types are calculated first, then a series of rules are applied to arrive at a single classification. The classification evidence bar is constructed using a point-based system which takes into account all evidence types relevant to the site type (NATURAL/CRYPTIC). The position of the bar within a single classification region reflects the balance between evidence supporting and contrasting the assigned classification. Supporting evidence moves the bar to the right, while contrasting evidence moves the bar to the left. If an equal amount of supporting and contrasting evidence types are present, the bar will appear directly in the middle of the region. The classification assigned to a case is made larger, bolded, and underlined. A classification evidence bar is present in the dropdown area for each case.

Additional Reclassification

Cases presented on ValidSpliceMut are grouped by variant, splice type (DONOR/ACCEPTOR), and site type (NATURAL/CRYPTIC). Cases are assigned a classification based on the effect of a variant on a single splice site "in a vacuum". However, the presence of an aberrant case in another site affected by the same variant, in the same tumour type, provides additional evidence the presence of the variant may produce an aberrant molecular phenotype. Thus, when displaying the predicted molecular phenotype classification for each case, classifications of other splice sites (NATURAL vs CRYPTIC) in the same tumour type affected by the same variant are also examined. If any of these other sites are classified as aberrant, all of them are reclassified as aberrant. In the event a reclassification has occurred, it is denoted as such below the classification evidence bar associated with the case.