Submission to ClinVar

• Know before you submit
  • Can I submit to ClinVar?
  • Do I need consent to submit?
  • How do I register to submit?
  • What data can I submit?
  • How many variants can I submit?
  • What data is required to submit?
  • Will ClinVar change my data?
  • Can I send a test submission?
  • How do I get a “star” for my submission?
  • How do I get accession numbers for a publication?
  • When will my submission be public?
  • What does ClinVar do with my data once it's public?
• Prepare your submission
  • Spreadsheet
  • tsv/csv files
  • Submission wizard
  • API
• Send your submission
• Update your submission
  • When can I update?
  • What information can I update?
  • How do I make the update?
  • How do I know which variants I've already submitted to ClinVar?

Know before you submit

Can I submit to ClinVar?

ClinVar welcomes submissions from:

• clinical testing labs
• research labs
• genetics clinics
• patient registries
• locus-specific databases
• expert panels
• groups establishing practice guidelines

Do I need consent to submit?

ClinVar assumes you have obtained appropriate consent to submit the data. Once the data are in ClinVar, they are available for unrestricted distribution.

How do I register to submit?

Submissions to ClinVar are attributed to organizations (not to specific people), so you should register your organization in the ClinVar Submission Portal. In your registration, you can also list personnel from the organization who should be listed publicly for the organization and you can authorize other people from the organization to submit data to ClinVar.

What data can I submit?

You can submit your classifications of a variant for a disease or a drug response.

• 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. Submission tip
• Some submissions do not include a variant classification, but they include another type of data that is critical for variant classification, including:
  • Submissions from clinicians or patient registries that provide clinical features observed in a patient
  • Submissions of functional data
  • Submissions that describe a variant in the literature
• ClinVar does not accept:
  • Large sets of uncurated variants 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.
  • Variants 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.

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.
• Submissions also include the evidence that supports the classification. Evidence may be:
  • aggregate data such as reporting different data for affected individuals vs unaffected individuals
  • case data about each individual with the variant, as long as the individual is not identifiable according to NIH guidelines
  • experimental evidence describing the functional impact of the varaint
• 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
    • Case data for each of the five individuals with the variant

How many variants can I submit?

A 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, please submit a separate classification for each variant
  • for example, most variants identified in compound heterozygosity should be submitted separately
• in a single submission file, you can provide one variant classification or thousands of variant classifications.
• 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.

What data is required to submit?

• submitter information including
  • the submitting organization
  • the person providing the submission
  • personnel at the organization who should receive public attribution for the submission
• a valid description of the variant, one of:
  • an HGVS expression
  • chromosome coordinates and change
• the condition for which the variant was classified
• the classification
• how the data were collected (collection method), e.g. from clinical testing or research
• allele origin, e.g. is the classification for a germline or somatic variant
• affected status, e.g. was the variant observed in individuals affected or unaffected by the condition for the classification

Your submission will be more useful to others if you also provide more supporting evidence, such as:

• number of observations of the variant
• mode of inheritance for the variant and condition
• zygosity of individuals with the variant
• ethnicity and/or geographic origin
• relevant citations
• a comment on classification explaining your rationale

Will ClinVar change my data?

In general, ClinVar does not change data that was submitted to the database. There are a few scenarios in which we change the format, but not the content, of data during submission processing:

• remove spaces from HGVS expressions, unless the space is between integers
• convert HPO: to HP: and report as HP:0000000 for an HPO identifiers
• modify "Location in gene" information according to ClinVar's conventions, including extra spaces, capitalization, abbreviations, and unsupported terms for "Location in gene"

The only instance in which ClinVar changes the content of a submitted record is the rare case where Personal Identifiable Information (PII) was included by the submitter.

• If PII is discovered during submission processing, NCBI staff will contact the submitter to remove the PII. No further processing of the submission will occur until the submitter removes the PII.
• If PII is discovered after a record is published, NCBI staff will remove the PII from the submission and notify the submitter. We will also remove the PII from past releases that include the submitted record.

Can I send a test submission?

We do not have a protocol for test submissions. Instead, your first submission can be a small representative set of data that you intend to make public. You will receive feedback and additional instructions to help you put together subsequent submissions for larger datasets. You can also send any questions about submission to [email protected].

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

Submissions to ClinVar are assigned a review status, based on the type of submitter. 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 below.
• 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 for your submission, 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", which 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 in 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 in 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 appearance of your ClinVar record, 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.

When will my submission be public?

Processing time for ClinVar submissions varies is typically about one week. Turnaround time partially depends on the quality of the data in submissions and the responsiveness of submitters to questions from the curation team, so we cannot guarantee turnaround time. We are unable to accommodate requests for submissions to be made public immediately, due to our submission process. We recommend starting your submission early (e.g. submit to ClinVar when you submit your manuscript to the journal) and reading our instructions for submission.

Also, you may experience delays in processing in August, late November, and December due to holidays/vacation schedules.

What does ClinVar do with my data once it's public?

Information about submitters

• Information about your organization will be made public on the website and in downloadable files.
• Information about you and others associated with that organization can be made public or kept private. Read more about public and private status for people.

Information about variant classifications

• All data for variant interpretations is aggregated with other submissions and made public in ClinVar’s public XML files.
  • This data is freely available for any use.
  • Some data are made public but are “fuzzed” to make the information less identifiable.
    • A specific age is converted to the appropriate decade.
    • A small region submitted as "Geographic origin" may be converted to a larger region, e.g. El Salvador may be converted to Central America.
• A subset of data is included in ClinVar’s VCF and tab-delimited summary files.
• A subset of data is displayed on ClinVar’s website.
• Novel variants submitted to ClinVar are also submitted to dbSNP or dbVar, as appropriate. Thus, submission to ClinVar is considered to be in compliance with NIH's Genomic Data Sharing policy.

Prepare your submission

More information is available in our FAQ about submitting to ClinVar.

Spreadsheet

Three Excel spreadsheet templates are available for submissions.

• To fill in the data, read our Instructions for ClinVar submission spreadsheets and the instructions in the spreadsheet itself.
• Do not edit the names of the worksheets or columns. Our processing of the spreadsheets depends on these names.
• Please 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. Please save 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

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.
• To fill in the data, read our Instructions for ClinVar submission spreadsheets and the instructions in the spreadsheet itself.

Submission wizard

If you have one variant classification to submit and would rather not fill out the spreadsheet, you can use the ClinVar single submission wizard in the Submission Portal. This 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 ClinVar submission wizard and our YouTube video.

API

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

Send your submission

1. Review the documentation and spreadsheet templates on the ftp site. If you have any questions, send them to [email protected].

2. Go to the ClinVar Submission Portal.

   • Register your organization first.
   • You will be notified by email when your organization is approved by ClinVar staff.
   • Then you can send submissions to ClinVar in the Submission Portal.

3. There are two options in Submission Portal:

   • If you are using one of the file formats described above, use the "Upload new file submission button" to upload your file(s).
   • If you are using the ClinVar single submission wizard, use the "ClinVar single submission wizard" button to enter your data online.

4. If you have any problems using the Submission Portal, please contact us at [email protected] so that we can help you with the process. If you have problem logging in to the Submission Portal, please contact [email protected].

5. We will contact you when a curator has reviewed your submission if we need clarifications or corrections. If you are unable to get back to us with those clarifications or corrections within one month, we will delete your submission. You can resubmit the data at any time.

Update your submission

When can I update?

You can update your submissions to ClinVar at any time. For example, you may want to update because:

• you have reclassified the variant
• you have determined the condition to associate with the variant
• you have more observations of the variant to describe
• you submit for a clinical testing laboratory and you want to send regular submissions, including both new submissions and updates, so that your laboratory's classifications do not become outdated in ClinVar.

What information can I update?

Any data point in a ClinVar submission may be updated.

• 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 with the submission spreadsheet template.

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. on the Variant tab

   • include the SCV accession number for your submission in the "ClinVarAccession" column
   • enter "update" in the "Novel or update" column

3. submit your spreadsheet as described above

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

To help keep track of your ClinVar submissions, 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