About

CVA Portal

CVA Portal is the GUI that provides access to the knowledgebase, it has 3 main pages:

1. Case View

   Provides an overview of a Rare Disease case in the knowledge base. The overview includes, where available the Summary of Findings (SoFs) and Reporting Outcomes Questionnaires (ROQs) and a list of phenotypically similar cases.

   In addition, it lists all the variants prioritised by the Interpretation Services applied to the case and whether these variants exist in other cases within CVA

2. Variant View

   Provides an overview of variants in CVA and includes the reported ACMG classifications of that variant in cases from the Genomics England Interpretation Platform. From the Variant View you can see all other cases in the Genomics England Interpretation Platform that also have this variant prioritised by Interpretation Services applied to them

3. Gene View

   Gene View provides an overview of all reported variants within a specific gene

How and When Does Data Get Into CVA?

Whole Genome Sequencing (WGS) rare disease analyses from the Genomics England 100K Project and NHS Genomic Medicine Service are automatically registered into CVA.

Results of Interpretation Services e.g. Tiering and Exomiser are added to CVA when they are registered in the CIP-API

Expert interpretations performed by NHS Clinical Scientists are automatically added to CVA in the form of Summary of Findings, Reporting Outcomes Questionnaires and Variant Interpretation Logs (VILs)

Interpreted Genomes

Interpreted genomes (IGs) are lists of variants which have been prioritised by algorithms (or "Interpretation Services", such as Exomiser or Tiering) in the GEL Rare Disease WGS pipeline.

We get any interpretation data as it is registered in CIPAPI from the Pipeline and case status is "To be reviewed" (where interpretations are yet to be made).

Summary of Findings

A Summary of Findings (SoF), or Clinical Report (CR) contains information on variants thought to be relevant to the patient's clinical presentation.

SoFs show the variant(s) in question, any associated genes, and the interpretation provided by the clinical scientist analysing the case.

We get SoFs when a user hits "submit" in the decision support system (DSS) or in the Interpretation Browser. Once the case's status is in "pending outcomes", the SoF is made available automatically in CVA (i.e. where an SoF has been generated but the RoQ is yet to be completed).

If a case has more than one SoF, only the latest is displayed

Reported Outcomes Questionnaires

After an SoF is generated, the user reviews and fills out the Reported Outcomes Questionnaire (RoQ).

RoQs contain diagnostic information such as the ACMG pathogenicity of the variant(s), any potential changes in patient treatment, and whether any additional testing was done.

Once completed and a user hits 'submit' the case status moves to the "reported cases tab" and it is automatically made available in CVA.

Variant Interpretation Logs

Variant Interpretation Logs (VILs) contain detailed information about the diagnostic interpretation of a variant, extracted from the Congenica Decision Support System. VILs show, among other things, the exact ACMG criteria applied to a variant, the clinical significance and computationally-calculated clinical significance, and any comments by the clinical scientist performing the diagnosis explaining their interpretation.

Please note, VILs are only available for variants that have an approved decision recorded against them and review completed in Congenica. If a variant has more than one VIL then all VILs are displayed, ordered by timestamp, with the most recently created VIL displayed first. Some older VILs may be missing timestamps.

Time of Day

All data is updated in CVA every day at 4am.

Known Issues

Variant Filter Bug

We are working to address an issue where the "Consequence type" filter on the variant search, case, and gene pages does not work correctly.

Specifically, the variant does not return the expected results when filtering for "2KB downstream variant" and/or "2KB upstream variant"