NOTE: Parts of this exercise work only using the Single-page view of Guide on the Side. Please switch to that view and adjust your windows to interact with the NCBI databases.

Single-page view

The NCBI ClinVar database collects reports from scientists on human genetic variants and their relationships to disease. Its purpose is to bridge genetic variation data and assertions about phenotypes.

You can search ClinVar with gene symbols, diseases, HGVS expressions, location on a chromosome, and more.

This tutorial is designed to help you answer the question:

How do I find specific disease-causing variants?

Example: What disease or condition is related to the CYP2C9*2 variant?

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Over the years, scientists have named gene variants in many different ways. NCBI has attempted to account for these various names by including them in the NCBI database records. Search ClinVar by the information you have, and use the database to uniquely identify the variant of interest.

In this case, we can only assume that CYP2C9*2 is a variant of the CYP2C9 gene. We'll search ClinVar for CYP2C9*2 and see if we can find a record that matches.

Search: CYP2C9*2

ClinVar search for CYP2C9*2

[Note: The asterisk (*) is not a wildcard in ClinVar.]

Example: What disease or condition is related to the CYP2C9*2 variant?

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You should see 36 or so records in your results for the search of CYP2C9*2 in ClinVar.

This results table provides basic information about the variation, the related gene(s), associated conditions, clinical significance and the review status.

CYP2C9 results

Let's look at the best matching record in more detail.

Click on the link labeled "CYP2C9*2"

Example: What disease or condition is related to the CYP2C9*2 variant?

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Let's first focus on the section of the record labeled HGVS. These are Human Genome Variation Society (HGVS) expressions for this variation.

Most ClinVar record titles are in HGVS nomenclature. This record happens to have a different title. But let's break down how to read the HGVS expression:

HGVS table in clinvar record

Looking at the item under Nucleotide starting NM:

NM_000771.4 refers to the reference transcript.

c.430 is the nucleotide position in the coding region of the reference transcript.

C>T means that the C at position 430 of the coding region of NM_000771.4 is changed to a T.

Under the Protein column:

NP_000762.2 refers to the protein reference record.

p.Arg144Cys refers to a resultant amino acid change in the protein.

HGVS expressions are standardized nomenclature for describing variations, so are incredibly useful in communicating about genetic variation. 

GRCh37 and GRCh38 refer to the specific assemblies of the human genome. These are Genome Reference Consortium Human Build 37 and Build 38.

Example: What disease or condition is related to the CYP2C9*2 variant?

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Click on the Conditions tab on the left and you will see details of the inherited and pharmacogenomic clinical assertions.

conditions tab

What clinical significance is associated with this variation in the CYP2C9 gene?

Example: What disease or condition is related to the CYP2C9*2 variant?

5 of 6Scrolling back up to the top of the record, note that ClinVar reports the level of review supporting the assertion of clinical significance for the variation as "review status."

review status

The stars reflect the level of agreement on the clinical assertion.

You can view the specific definition of each review status in the ClinVar documentation.

What do the number of gold stars on this particular record mean?

Example: What disease or condition is related to the CYP2C9*2 variant?

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You have reached the end of this tutorial on ClinVar.

Continue to the Clinical Applications Quiz

Return to the Moodle course page

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