How can I submit to ClinVar?

This article guides you through the process of submitting to ClinVar from VarSome, VarSome Premium or VarSome Clinical. 

Submitting from VarSome.com

Step 1

Register on the ClinVar Submission Portal.

This requires you to provide information about the submitting organization and the people associated with that organization.

Request a service account

Submission by API requires a Service account for the submitting organization and an associated API key. Please contact clinvar@ncbi.nlm.nih.gov to request a Service account. You need to provide an email address that you want to be associated with the service account.

Both of these actions are mandatory for using this feature. Any existing VarSome user/organization must already be registered and logged in to the application in order to submit to ClinVar.

Step 2 

Search for the variant of interest on VarSome starting from one of the two options (1) and Click on the "Submit to ClinVar" button (2) available on the Variant page:

- Home page

- Variant page

 

The "Submit to ClinVar" button is available in the sub navigation bar as seen on the screenshot above, and also inside the ClinVar component:



 

NOTE: Once you click on the submit button, if you have not previously configured the ClinVar API key, you will get a message prompting you to do so:

Step 3

Complete the Submission  form.

Assertion Criteria

In order to submit to ClinVar you will have to provide evidence describing the criteria you use to classify variants. This is called "Assertion criteria". During this step, you will have to provide a short name for your assertion criteria that you want displayed on the ClinVar website (1) and the assertion Method Citation (2). As seen below it may be a single citation,url or a file name.

Clinical Significance

Here you reference citations that were used to evaluate the clinical significance of the variant. More than one citation may be provided (1). Each citation can be provided as a database identifier, like a PubMed ID, or a URL, but not both.

NOTE: In cases where you provide the Citation ID, and it’s origin is from PubMed, our system will validate it and display the Abstract to you.

Next, you need to select a significance description which concerns the interpretation, or clinical significance, of the variant for the submitted condition, equivalent to clinical significance in the submission spreadsheet. 

 

You can also provide extra evidence to support the classification given with a comment describing the rationale for the clinical significance (2), as well as the date that the clinical significance was last evaluated by the submitter (not the date the phenotype of the patient was evaluated), equivalent to date last evaluated in the submission spreadsheet. Please use the yyyy-mm-dd format. If only month/year is known, use the first day of the month. If only year is known, use Jan. 1.(3)
Submitters should provide a value for clinical significance in the context of a submitted mode of inheritance (4).

 

Condition(s) set

The next section is about the condition for which the variant is interpreted. The condition must be provided as either a database identifier (OMIM, Orphanet, MedGen etc) or a name, but not both (1).

You have the option to enter the condition with your Local Id your organization uses to identify this variant or your Local Key, your unique local identifier for the variant-condition pair, equivalent to the Linking ID in the submission spreadsheet.(2)

 

Observed In

Additionally, it is necessary to provide supporting evidence about the affected status which indicates whether or not the individual(s) in each observation were affected by the condition for the interpretation, as well as the allele origin(1).

 



If you would like to add Clinical Features please click first on ‘’Add Clinical Feature button’’.

 




Clinical Features that were observed by the submitter in an individual with the variant can be described in this section, optionally. More than one feature may be provided and each clinical feature may be described by a database identifier or by a name, but not both.

 

The collection method describes the setting in which the variant interpretation is made and it’s necessary to provide data to users of ClinVar to understand the collection method procedure(2).

 

You also have the option to provide a free text explanation of clinical features provided in the previous column, e.g. to describe the progression of disease or diagnosis. Please use this comment to expand on the information in 'clinicalFeatures'. It is suggested to mention, if possible, the total number of individuals with the variant observed by the submitter as well as the method and type of analysis used to identify a structural variant (3).

 


The following section is about submission name(1), record status(novel/update,mandatory field)(2),and the release status(Public/hold until published)(3).

Submission name if not provided, it will be the submission id.

 

 

Variant Set

The interpreted variant must be described either by HGVS or by chromosome coordinates, but not both.

We currently do not support the submissions of CNVs but our intention is to release this option in the future. 



 

Once you have provided all necessary information please click Submit. You have the option to track all your submissions in the ClinVar submissions section of your Profile.



This will display a list of all submissions made by your organization using the organization ClinVar API key. It will also allow you to track their date of submission, status or be notified of any submission errors.


There are 5 possible statuses for each submission:

  • Submitted
  • Processing
  • Error
  • Processed but not published on ClinVar
  • Published on ClinVar


Submitting from the clinical platform

Step 1

Please log into VarSome Clinical, go to the front page (1) and select one of your latest analyses as shown below (2).

 

NOTE: Before you proceed please make sure that you agreed to the terms of access (screenshot below).

Step 2

Select the variant of interest from the results table (1) and click on the ACMG component (2) available on the Varsome Clinical results analysis page.

Then click on the "Submit to ClinVar" button (3), which is available inside the ACMG component:

 

NOTE: The following steps on how to populate the form are completely identical as previously described in the “Submitting from VarSome.com” part of the documentation.

Step 3

After Submitting to ClinVar, same as in VarSome.com, you will be able to see all submissions you have made, track their status (1) or tackle any potential submission errors.

 

If additional help is needed, depending on the type of the issue you might be experiencing, you can always email us at support@varsome.com or contact ClinVar directly on clinvar@ncbi.nlm.nih.gov.