Submission instructions

• Data preparation
• File submissions
• Single submission wizard
• API submissions
• Updating your records
• Deleting a record

Data preparation

Each submission to ClinVar is a classification of a variant for an inherited disease, cancer type, or a drug response.

• The classification should be a variant-level classification for a disease or a drug response, not a case-level (or patient-specific) interpretation.
• Submissions to ClinVar are considered "variant-level", because they are focused on the variant or set of variants that were classified.
• Each submission also includes one or more observations of the variant that support the classification. Observations may be:
  • a single aggregate observation of the variant in one or more individuals
  • one or more case-level observations for each individual with the variant, as long as the individual is not identifiable according to NIH guidelines
  • one or more observations of the variant in a functional assay performed by the submitter

• Example: if you have classified a variant that you observed in five individuals:

  • Submit your current classification of the variant
  • Submit your evidence as either:
    • Aggregate data for the group of five individuals with the variant
    • or as Case-level data for each of the five individuals with the variant

• Variants that were autoclassified as Benign due to allele frequency may be submitted as long as the variants were observed by your organization as part of your clinical testing, research, etc. Read our recommendation for submitting autoclassified variants.

• Some submissions do not include a variant classification; they are focused on a type of evidence that is critical for variant classification, including:

  • clinical features observed in a patient, typically submitted by a clinician or patient registry
  • functional data
  • citations in the literature

• ClinVar does not accept:

  • Variants with a statistical association for a disease, such as from GWAS studies. Submit these data to dbGaP.
  • Variants that were observed in a patient but not classified for a disease or a drug response. Submit these data to dbSNP or dbVar, as appropriate.
  • Variants with classifications based solely on computational predictions.
  • Submissions that include Personal Identifiable Information (PII). PII should not be included anywhere in a ClinVar submission. If PII is missed during the submission review process and discovered later, ClinVar will remove the PII. See Will ClinVar change my data?
• A small number of fields are considered the minimal fields for a submission.

How many variants can I submit?

In a submission file or API submission, you can provide one variant classification or thousands of variant classifications.

Each classification may be for

• a single variant
• a set of variants that were classified together, as a haplotype or a genotype
  • if the variants were observed together but can be classified independently, submit each variant separately with its own classification
  • for example, most variants identified in compound heterozygosity should be submitted separately
• ClinVar does not accept "individual-level" data such as an entire set of variants identified in a single individual. Please submit that data to dbGaP.

How do I get a “star” for my submission?

Submissions to ClinVar are assigned a review status, based on the type of submitter and the information provided in the submission. The review status is also represented on the website by gold stars.

For a one-star submission:

• Read our description of assertion criteria.
• Read our instructions for how to include this information in your submission.

For a three- or four-star submission:

• Read our guidelines for applying for “expert panel” or “practice guidelines” status in ClinVar.

How do I get accession numbers for a publication?

• Submit early in the publication process, e.g. before acceptance of the manuscript. We cannot guarantee the processing time for a submission.
• Provide your complete submission as described in our submission instructions.
• Accession numbers are assigned per variant classification, not for the entire submission. We must have valid data for all required fields for each classification to assign accession numbers.
• In the Submission Portal, answer yes to the question "Do you need ClinVar accession numbers before processing is complete (e.g. for a publication)?"
• We will give you ClinVar accession numbers which begin with SCV and are searchable in ClinVar.
  • You can cite these accessions in your publication.
  • The submission identifier (SUB id) may be cited if you retained this identifier as the submission name. If not, this identifier is not searchable in ClinVar.
  • Do not cite identifiers that begin with MDI; these are not searchable in ClinVar.
• You can also provide a submission name in the Submission Portal. The submission name can be included in your publication and be used to retrieve from ClinVar the complete set of accessions belonging to the submission.

If you also need your data to be held private until the paper is published:

• select "Hold until published" as “Release status” in the Submission Portal
• we will assign accessions for your submission, which you can include in your publication
• we will hold your data private until
  • you or the journal notifies us of the publication or
  • we notice the paper is published in the journal or another public database or
  • six months have passed after the time of submission; we cannot hold a submission indefinitely

To prevent a delay in the release of your ClinVar submission, we urge submitters to contact us with the PubMed ID for the publication as soon as it is available.

You may also submit your data after publication. In this case, please include the citation in your submission.

File submissions

Excel spreadsheets

Four Excel spreadsheet templates are available for submissions.

• Download the templates from the ClinVar FTP site.
• Use the table below to choose which template is right for your submission.

Tips for using the templates:

• Basic instructions are provided in the templates themselves, and additional details are provided in our instructions for ClinVar submission spreadsheets.
• Do not edit the names of the worksheets or columns. Our processing of the spreadsheets depends on these names.
• Use the most recent version of the spreadsheet to expedite processing of your submission.
  • The spreadsheet templates have version numbers on the SubmissionInfo tab.
  • Updates to the spreadsheet templates are documented in a README file on the ftp site
• We only accept .xlsx files, not .xls or xlsm. Save your files with the latter formats as .xlsx before submitting to ClinVar.
• Use a browser other than Safari to download the templates.
  • Safari will probably redirect you to Finder, and give you the impression that you need credentials for the FTP site.
  • You do not need login credentials to access content on ClinVar's FTP site.
  • You will not encounter this problem with Firefox or Chrome.

tsv/csv files

Alternatively, you can submit your data in tsv or csv files that are based on the columns in the spreadsheet templates.

• Choose a base name for all files in your submission
• Create a set of files, each with the same base name and corresponding to each tab in the spreadsheet
  • e.g. a submission based on SubmissionTemplateLite.xlsx has the following files:
    • FILENAME.Variant.csv
    • FILENAME.ExpEvidence.csv
  • e.g. a submission based on SubmissionTemplatel.xlsx has the following files:
    • FILENAME.Variant.csv
    • FILENAME.CaseData.csv (optional, if case data is provided as evidence)
• Note that the file names are case-sensitive, e.g. FILENAME.Variant.csv, not FILENAME.variant.csv
• Include the column headers exactly as in the spreadsheet in the first line of each file.
  • You only need to provide column headers for columns where you provide data.
    • e.g. if you only submit the required fields, only those columns need to be in the file
  • The order of the columns does not matter.
• Fill in the data as for a spreadsheet submission.

Upload your submission

• Once your file submission is ready to submit, go to the ClinVar Submission Portal and use the "Upload new file submission button" to upload your file(s).
• If you have any problems using the Submission Portal, contact us at [email protected] so that we can help you with the process.
• If you have problems logging in to the Submission Portal, contact [email protected].

Single submission wizard

• In the ClinVar Submission Portal, click the button for "ClinVar single submission wizard"
• The single submission wizard guides you through submission of a single classification at a time, prompting you to describe the variant, the condition, your classification, and the supporting evidence.
• See the help documentation for the submission wizard and our YouTube video.

API

If you would like to automate your submissions, you can submit via our submission API.

Update your records

When can I update?

You can update your records in ClinVar any time after they are public. For example, you may want to update because:

• you reclassified the variant
• you determined the condition to associate with the variant
• you observed the variant in more individuals
• you generated functional data for the variant
• you identified more citations for the variant

What information can I update?

Any data point in a ClinVar record may be updated by the submitter.

• If you are updating the description of the variant because it was incorrect, the submission is assigned a new SCV accession number.
• If you are updating any other type of data, the submission retains the same SCV accession number.
• You may also merge together two redundant submissions or delete submissions, if necessary.

How do I make the update?

If you want to update the classification for a single variant:

Use the option for Single SCV Update in the ClinVar Submission Portal.

1. Enter the SCV accession number for your record
2. Update one or more of the following fields:

   • The classification of the variant
   • The assertion score
   • The date that the variant was last evaluated
   • The comment on classification
   • The mode of inheritance for the variant and disease
   • The condition for which the variant was classified
   • Citations on classification

3. Review the update for your record and submit

If you have several variants to update, or you need to update fields other than those listed above:

Submit your update in a file or API submission.

1. Provide all information for the variant classification, including the updated information
   • the update overwrites your previous submission, rather than adding to it, so include all previous information that you want to retain
2. Include the SCV accession number for your submission
   • for a file submission, use the "ClinVarAccession" column on the Variant tab
   • for an API submission, use clinvarAccession
3. Enter "update" in the "Novel or update" field
   • for a file submission, use the "Novel or update" column on the Variant tab
   • for an API submission, use recordStatus
4. Submit your spreadsheet as usual

How do I know which variants I've already submitted to ClinVar?

To help keep track of your ClinVar variants, you can generate a cumulative report of all records from your organization assigned a ClinVar accession and released publicly, including records that were deleted subsequently. Records that are being processed or are being held until publication are not included in the report.

1. In the ClinVar Submission Portal, use the button for "Cumulative Report of Released Records".
2. Your report is generated on-the-fly; if your organization has many records, this may take several hours to produce.
3. A link to the report will be emailed to you.

Deleting a record

Occasionally, you may need to delete one of your records in ClinVar, for example, if the variant description was in error.

Use the "Deletes" worksheet on the full submission template (SubmissionTemplate.xlsx), the somatic submission template (SubmissionTemplateSomatic.xlsx), or the functional data template (SubmissionTemplateFunctionalData.xlsx).

• In the "ClinVar Accession" column, provide the SCV accession numbers for the records to delete.
• We recommend that you provide an optional explanation for deleting the record in the "Comment" column.
• If you do not provide a comment, a generic reason will be provided: "This record was deleted at the request of the submitter."
• Note that you can only delete your own SCV records; you cannot delete SCV records owned by another submitter.