Overview:

ClinGen has a list of approximately 100 “high priority” genes, including the ACMG 56 genes related to actionable secondary findings on exome sequencing. Many of the genes are associated with the conditions most frequently submitted to ClinVar. In many cases, different ClinVar submitters use different names for the same condition. This can be a source of confusion among users of the ClinVar database.

The ClinGen Phenotype Working Group has tried to address this problem by developing a list of preferred condition names for the ClinGen priority genes. Standardizing the condition name associated with a particular gene or variant will improve the ability of users to search ClinVar for variants associated with that particular condition.

The most recent version of the Preferred Condition list and instructions on how to use the document are included below. We encourage ClinVar submitters to use this document to inform their ClinVar submissions. Submitters who use other condition names may receive feedback after the submission in an effort to improve uniformity in the database. This document will be updated as the Phenotype WG works to compile a list of preferred terms for additional genes.

How to use the Preferred Condition List:

If the variant your laboratory is submitting to ClinVar is located in a gene related to a condition which appears on the ClinGen Preferred Condition list, we ask that you select a Level 1 condition term as the condition associated with your submission. Level 1 terms are more specific condition names.  If you are unable to choose a Level 1 condition, please select a more general Level 2 condition name.

Once you have selected the appropriate term from the list, complete BOTH the “Condition ID Type” and “ID Value” fields in the ClinVar submission template. If a condition name is selected from the Preferred Condition list, then the “Preferred Condition Name” field on the submission form should be left empty.

If the Level 1 or Level 2 terms do not represent the condition assertion for the variant, select a different ID type and value to use or simply enter the name of the condition in the “Preferred condition name” field.

Example: If you are trying to submit an assertions for a CDKL5 variant with regards to Atypical Rett syndrome, you would submit the following in the ClinVar submission spreadsheet:

  • Note that BOTH the “Condition ID Type” and “ID Value” should be submitted.

Gene

Reference Sequence

HGVS

Condition ID Type

ID Value

Preferred condition name

CDKL5

NM_003159.2

c.1675C>T

MedGen

C0393706

 

If the preferred term is followed by a "***", this indicates that the condition is associated with somatic variants. For these conditions, please specify the allele origin (germline or somatic) in the contect of a clinical significance interpretation when submitting to ClinVar (ClinVar submission template- "allele origin").

Preferred Condition List- Version 3.0 - Updated September 2016