Review status in ClinVar

Review status

Definition

ClinVar reports the level of review supporting the assertion of clinical significance for the variation as review status. Stars provide a graphical representation of the aggregate review status on web pages. Table 1 provides definitions of each review status and the corresponding number of stars. Review status is reported in text format in ClinVar's products available by ftp

Table 1. The review status and assignment of stars 

Number of gold stars Review status Description
four practice guideline practice guideline
three reviewed by expert panel reviewed by expert panel
two criteria provided, multiple submitters, no conflicts Two or more submitters with assertion criteria and evidence (or a public contact) provided the same interpretation.
one criteria provided, conflicting interpretations Multiple submitters provided assertion criteria and evidence (or a public contact) but there are conflicting interpretations. The independent values are enumerated for clinical significance.
one criteria provided, single submitter One submitter provided an interpretation with assertion criteria and evidence (or a public contact).
none no assertion for the individual variant The allele was not interpreted directly in any submission; it was submitted to ClinVar only as a component of a haplotype or a genotype.
none no assertion criteria provided The allele was included in a submission with an interpretation but without assertion criteria and evidence (or a public contact).
none no assertion provided The allele was included in a submission that did not provide an interpretation.

Each record in ClinVar is assigned a review status, including:

  • SCVs, or submitted records
  • RCVs, or aggregate variant-disease records
  • Coming soon: VCVs, or aggregate variant records (equivalent to the Variation ID)

The review status for a submission (SCV) is determined by the data provided in that submission, as detailed below (Requirements for higher review statuses).

The review status for an aggregate record (RCV or VCV/Variation ID) depends on data provided in all of the contributing SCVs:

  1. whether any submission provided assertion criteria and evidence (or a public contact)
  2. whether the submissions agree on the interpretation
  3. the review status from an expert panel or a practice guideline submission becomes the review status for the corresponding aggregate records

Web display

The aggregate review status for the Variation ID is displayed on the variation report as in Figure 1. Gold stars are also used to represent the aggregate review status on web pages. Note that there are multiple review statuses represented by zero and one stars; see the correlation between review status and stars above.

Figure 1. Aggregate review status for the Variation ID.

ClinVar variation report - review status

FTP

The review status is included in FTP files as follows:

File How review status is reported
ClinVarFullRelease XML

Review status for the RCV is reported as:

<ReferenceClinVarAssertion>
   ...
   <ClinicalSignificance>
      <ReviewStatus>criteria provided, single submitter</ReviewStatus>
   </ClinicalSignificance>
   ...
</ReferenceClinVarAssertion>

Review status for the SCV is reported as:

<ClinVarAssertion>
   ...
   <ClinicalSignificance>
      <ReviewStatus>criteria provided, single submitter</ReviewStatus>
   </ClinicalSignificance>
   ...
</ClinVarAssertion>
VCF

New VCF files (VCF 2.0) report review status for the Variation ID in the CLNREVSTAT INFO tag.

Old VCF files reported review status for each RCV for the rs ID in the CLNREVSTAT INFO tag.

variant_summary.txt

The ReviewStatus column reports the highest review status for each variant.

summary_of_conflicting_interpretations.txt

The review status for each of a pair of conflicting submissions is reported as Submitter1_ReviewStatus and Submitter2_ReviewStatus.
submission_summary.txt The review status for each submission is reported as ReviewStatus.

Assertion criteria

Definition

“Assertion criteria” refers to a publication or other electronic document (such as a Word document or PDF) that describes the variant assessment 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 interpretation process, not the specific evidence for an individual variant interpretation.

Note that for the purpose of calculating review status in ClinVar, both assertion criteria AND either evidence for the interpretation OR a public contact person are required. Please see the requirements for review statuses for more details.

Representative documentation of assertion criteria

These examples are provided to help submitters understand what is meant by documentation of "assertion criteria" and guide you in creating your own documentation for your specific assertion criteria. These 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).

Type of documentation Example
Assertion criteria GeneDX Variant Classification (06012015)
Expert panel 2013-08_InSiGHT_VIC_v1.9.pdf

Requirements for higher review statuses

Single submitter, criteria provided

An organization may achieve the "single submitter, criteria provided" status by meeting the requirements for this status in their ClinVar submission.

Expert panel or practice guideline

An organization wishing to achieve the expert panel or practice guidelines status must first be approved by ClinGen. Interested organizations are encouraged to contact ClinGen early in the application process, before completing the application form that can be downloaded from our ftp site.

How to provide assertion criteria in your submission

Assertion criteria can be provided:

Assertion criteria may be provided as a citation (such as a PubMed ID), a URL, or a file. For assertion criteria provided as a file, ClinVar generates a URL to make the file publicly accessible.

Some recommendations naming 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

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 Variation ID pages in the Assertion and evidence details, in the Clinical Assertions tab, as in Figure 2.

Figure 2. Links to assertion criteria on a Variation ID page, labelled as “Assertion method”.

ClinVar variation report - assertion criteria

Assertion criteria can also be accessed per organization on each submitter page, e.g. the submitter page for Counsyl  in Figure 3:

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

ClinVar - submitter page example

FTP

Data for assertion criteria for each submission are available in the XML file for RCVs (ClinVarFullRelease) and in the beta release of the new variant-centric XML (ClinVarVariationRelease). Both XML files use the AttributeSet structure for assertion criteria. The Attribute includes the name of the assertion criteria, and a URL to access the document.

File

How assertion criteria is reported

ClinVarFullRelease XML

Assertion criteria for each submission (SCV) is reported as:

<ClinVarAssertion>

   ...

   <AttributeSet>

      <Attribute Type="AssertionMethod">Ambry Autosomal Dominant and X-Linked criteria (10/2015)</Attribute>

      <Citation>

         <URL>https://submit.ncbi.nlm.nih.gov/ft/byid/aH4uL7vL/mid-7377_ambry_classification_scheme_oct_2015.pdf</URL>

      </Citation>

      </AttributeSet>  

   ...

</ClinVarAssertion>

ClinVarVariationRelease XML

Assertion criteria for each submission (SCV) is reported as:

<ClinicalAssertion>

   <AttributeSet>

       <Attribute Type="AssertionMethod">Ambry Autosomal Dominant and X-Linked criteria (10/2015)</Attribute>

       <Citation>

         <URL>https://submit.ncbi.nlm.nih.gov/ft/byid/aH4uL7vL/mid-7377_ambry_classification_scheme_oct_2015.pdf</URL>

       </Citation>

     </AttributeSet>

</ClinicalAssertion>

Last updated: 2017-09-26T12:46:50-04:00