Review status in ClinVar

• Review status
  • Definition
  • Review status on submitted records (SCV)
  • Review status on aggregate records (VCV and RCV)
  • Web display
  • FTP
• Assertion criteria
  • Definition
  • How to provide new assertion criteria
  • How to specify assertion criteria for your submission
  • Web display
  • FTP

Review status

Definition

ClinVar reports the level of review supporting the variant classification for the variation as review status. Gold stars provide a graphical representation of the aggregate review status on web pages. Review status is reported only in text format in ClinVar's products available by FTP.

Review status on submitted records (SCV)

Review status on submitted records (SCVs) is assigned as follows:

Review status on aggregate records (VCV and RCV)

ClinVar calculates a review status for each type of classification on aggregate records, both VCV (variation) and RCV (variation-condition) records.

Germline classification and oncogenicity

Review status for germline classification and oncogenicity on aggregate records (VCV and RCV) is assigned based on data provided in the contributing SCVs:

1. if there is a submitted record from a practice guideline or an expert panel, the review status from the submitted record (SCV) is used for the VCV and RCV records
2. otherwise, the review status is based on a. transparency: whether any submitted record provided assertion criteria and evidence for the classification (or a public contact) and b. consensus: whether the submitted records agree on the classification

The review statuses for germline classification and oncogenicity on aggregate records are as follows:

Somatic classification of clinical impact

Review status for somatic classification of clinical impact on aggregate records (VCV and RCV) is assigned based on data provided in the contributing SCVs.

It differs from the calculation for germline and oncogenicity in that consensus in the classification is not considered. The rationale is that for a given variant, it will be typical for different tiers to be reported for different types of assertions (therapeutic, diagnostic, or prognostic) and different tumor types, so conflicts are not informative. Thus the review status for somatic clinical impact is based on the following data provided in the contributing SCVs:

1. if there is a submitted record from a practice guideline or an expert panel, the review status from the submitted record (SCV) is used for the VCV and RCV records
2. otherwise, the review status is based on a. transparency: whether any submitted record provided assertion criteria and evidence for the classification (or a public contact) b. multiplicity: whether there are multiple submitted records (consensus is not required)

The review statuses for somatic classification of clinical impact on aggregate records are as follows:

Web display

The aggregate review status for each type of classification for a VCV record is displayed at the top the VCV page in the Classification summary, with words and with gold stars.

Note that there are multiple review statuses represented by zero and one stars; see the correlation between review status and stars above.

FTP

The review status is included in FTP files as shown below.

Assertion criteria

Definition

Assertion criteria refers to a citation (PubMed ID, PubMedCentral ID, or DOI) or an electronic document (a Word document or PDF) that describes:

• the variant classification terms used by the submitter (e.g. pathogenic, uncertain significance, benign, or appropriate terms for other types of variation) and
• the criteria required to assign a variant to each category

This document describes the categories and criteria that are used by the submitter to guide their classification process, not the specific evidence for an individual variant classification. This document is made available to ClinVar users on Clinvar web displays.

Note that when assertion criteria are provided, it is presumed that the submitter attests that the variant was classified according to a comprehensive review of evidence consistent with, or more thorough than, current practice guidelines. Read more details about meeting the requirements for the "criteria provided, single submitter" review status.

Representative documentation of assertion criteria

The following table provides examples to help submitters understand what is meant by documentation of assertion criteria and to guide you in creating your own documentation for your specific assertion criteria. These example documents are not intended to be submitted to ClinVar by other groups; please do not include either of these documents in your submission (unless your group provided the sample documentation).

Examples of submitted assertion criteria.

How to provide new assertion criteria

For a citation:

• Wizard or file submission: in the ClinVar Submission Portal, on the submission's "Assertion method" tab, select the option to "use a new assertion criteria".
• API submission: a citation is provided in the JSON, as described in the API documentation.

For a file:

Files for assertion criteria are uploaded independent of submissions. On your organization's landing page in the ClinVar Submission Portal use the button "View/add assertion criteria files" below your organization's name to upload a new file. ClinVar generates a URL to make the file publicly accessible on ClinVar web displays.

Some recommendations to name your assertion criteria file:

• use an informative name, including the name of your organization
• include a version number or a date; assertion criteria are likely to be updated over time and ClinVar requires distinct names for distinct files
• if you have multiple documents for different scenarios, for example one document for autosomal recessive variants and one for autosomal dominant variants, include that information in the name
• if your methods are published but not open access, please excerpt the variant interpretation methods from the publication and submit with reference to the full publication

How to specify assertion criteria for your submission

Wizard or file submission: in the ClinVar Submission Portal, on the submission's "Assertion method" tab:

• select the option to "use one of my existing assertion criteria"
• choose the desired citation or file

API submission: a citation or URL for a file already uploaded in the Submission Portal is provided in the JSON, as described in the API documentation.

A submission must reference one set of assertion criteria only, and these criteria must apply to every variant classification in the submission.

Remember that the review status of "criteria provided, single submitter" requires this documentation AND either the evidence for each interpretation OR a public contact for your organization.

Web display

Links to assertion criteria for each submission are displayed on the Variation ID pages in the "Submitted interpretations and evidence" section of the "Variant details" tab as shown in Figure 2.

Figure 2. Links to assertion criteria on a VCV record.

Assertion criteria can also be accessed per organization on each submitter page as shown in Figure 3.

Figure 3. An example of a submitter page with links to assertion criteria for that organization.

FTP

Assertion criteria are availabe in the RCV and VCV XML files as shown in the following table.

Assertion criteria in ClinVar's FTP files.