FAQ about submitting data to ClinVar

Getting started

1. Can I submit by API?
2. Which spreadsheet should I use?
3. Do I have to fill out all the tabs?
4. The spreadsheet template has a lot of columns; I don't know where to start.
5. I'm submitting my research on a clinically relevant variant for publication. Can I submit the data to ClinVar?
6. There is already a record in ClinVar for a variant that I intended to submit. Should I submit it too?
7. Can computational predictions of pathogenicity be submitted to ClinVar?

Getting into the details

1. I am not certain how to report disease or phenotype. Where do I begin?
2. Can I submit allele frequency data?
3. How does ClinVar know if my submission is novel or an update to what I submitted previously?
4. How do I delete a record that I've submitted to ClinVar?
5. Which resources can I reference in my ClinVar submission?
6. Can I submit a genotype?

Getting started

Can I submit by API?

Yes! Please read our documentation for the ClinVar submission API.

Which spreadsheet should I use?

For germline variants, there are two options.

• Most submitters will find the full spreadsheet, SubmissionTemplate.xlsx, to be appropriate. There are a small number of required fields; after that, you can provide as many other data types as you would like to submit, such as the number of individuals with the variant, zygosity, or clinical features.
• If you are providing minimal data, you can use SubmissionTemplateLite.xlsx. It has the same required fields as the full template but with fewer options for additional data. Keep in mind that submissions with more supporting evidence are more useful for ClinVar users.

Do I have to fill out all the tabs?

All submitters need to fill out the Variant tab. This tab should include each unique variant-condition pair and the classification, one per row.

If you are using SubmissionTemplate

• You can submit aggregate-level supporting evidence, such as the allele origin or the number of individuals with the variant, on the Variant tab also.
• Alternatively, you can use the CaseData tab to provide information about each individual observed with the variant. The information is provided on CaseData as one individual per row.
• For each variant-condition classification, please provide *either* aggregate data on the Variant tab *or* individual data on the CaseData tab, to avoid over-counting individuals.
• The FunctionalEvidence tab is optional and is intended for laboratories that submit functional data, such as animal models or in vitro cellular assays, to support variant classification.

If you are using SubmissionTemplateLite

• you also need to fill out the ExpEvidence tab to provide your aggregate-level supporting evidence for each classification.
• For example, you can provide total counts for the number of times a variant has been observed, or you can provide aggregated counts broken down by variables such as sex, age range, or affected status.

The spreadsheet template has a lot of columns; I don't know where to start.

If you are submitting a single variant classification, consider using the ClinVar submission wizard which guides you through the submission.

If you are submitting more than one variant on the spreadsheet template, consider starting with the required columns, as there are a small number of these.

After that, consider what data you have readily available and how that relates to fields requested by ClinVar. Also note what data types you find useful as a ClinVar user, and consider if you are able to provide that data for your own submission. You can use Excel’s function to hide any columns that you don’t use in your submission to make the template easier to use.

If you need assistance mapping your data fields to ClinVar's, please contact us at [email protected].

I'm submitting my research on a clinically relevant variant for publication. Can I submit the data to ClinVar?

Yes, ClinVar welcomes submissions from research labs as well as from clinical testing labs. Submissions from research labs should use the collection method "research". We can hold your submission until published (see our hold until published policy and we can provide ClinVar SCV accession numbers that can be included in your publication.

There is already a record in ClinVar for a variant that I intended to submit. Should I submit my data for that variant too?

Yes, you can submit your own classification of a variant that is already in the database. Each additional submission adds value to the community curation of that variant by noting additional evidence and approaches to classification.

Can computational predictions of pathogenicity be submitted to ClinVar?

Variants that are classified based solely on computational predictions are not appropriate for ClinVar. Submissions that use software for pathogenicity prediction as part of the overall assessment are welcome; we encourage you to indicate the name of the software in your submission as part of the methods.

Getting into the details

I am not certain how to report disease or phenotype. Where do I begin?

Please see ClinVar's recommendations for how to report a disease or phenotype in a submission.

Can I submit allele frequency data?

ClinVar imports allele frequency data from sources including Gnomad, the 1000 Genomes Projectm and TopMed, so these data do not need to be included in your submission. Frequency data that are not otherwise publicly available may be submitted; use collection method “reference population”.

How does ClinVar know if my submission is novel or an update to what I submitted previously?

When you submitted to ClinVar, you received an accession starting with SCV that uniquely identifies each variant classification. When you need to update your classification in ClinVar, you should include the SCV accessions in your update submission and indicate that the variant is an update in the "Novel/update" column on the Variant tab.

If the SCV accession is not included in the update submission, we presume that you are submitting a novel record. However, we may see data in your submission that suggests that you meant to update a record instead of submitting a novel record:

• a LinkingID that you have submitted before
• a combination of local ID and condition that you have submitted before
• a combination of variant and condition that you have submitted before

For these cases, you will get an error in pre-submission validation. Contact us at [email protected] if you are uncertain how to to address this type of error.

How do I delete a record that I've submitted to ClinVar?

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

• In the "ClinVar Accession" column, provide the SCV accession numbers for the records to delete.
• You have the option of providing an 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.

Can I submit a genotype?

You can submit a genotype to ClinVar, but in most cases this is not appropriate. ClinVar is a database of variant-level classifications, not patient-level interpretations. So the majority of classifications in ClinVar are for individual variants, even if a variant was observed in combination with another variant.

Compound heterozygotes

In general, if you classified two variants in trans, the two variants should be submitted individually to ClinVar, each variant with its own classification. This makes it easier for others to find data in ClinVar for each individual variant, and it makes the classification for each variant clear. A classification for the compound heterozygote is acceptable if the combination of the two variants is important for the classification, e.g. typically each variant is benign but the combination is pathogenic. This case is expected to be very rare.

Note that in ClinVar, a "compound heterozygote" refers to an individual with two variants in trans that are both considered pathogenic or likely pathogenic. Data for a heterozygote with two variants in trans that are of uncertain significance should be submitted as separate records, one for each variant.

Homozygotes

If you classified a variant that was observed in homozygosity, the variant should be submitted as a single variant, not as a genotype with the variant in homozygosity. You can indicate in the observation data that the variant was observed in homozygosity. Mode of inheritance should also be provided, e.g. submit "autosomal recessive inheritance" to indicate that while the variant is classified as pathogenic, a single copy of the variant does not cause disease.