ClinGen Aggregated Sequence Variant IRB Template
Title: Genomic Data Sharing to Improve Health
Sponsor Name: NIH
Purpose
Genomic variation underlies almost all human disease. Technological advances are quickly
making variant detection across the genome commonplace in the medical care environment,
sparking an expansion of both basic and clinical research. At this time, however, our ability to
detect DNA variation has greatly surpassed our ability to interpret the clinical impact of these
variants, particularly given the lack of publicly available, carefully curated information on
variants and phenotypic consequences. Although collections of some disease-associated variants
are available in certain online mutation databases, the variant annotations are limited, often
inaccurate and subject to inconsistent standards. In contrast, carefully curated disease-associated
variants from patient populations evaluated by individual clinical laboratories are often
sequestered in internal laboratory databases making them unavailable to the community.
To address these challenges, the National Center for Biotechnology Information (NCBI) in
collaboration with the Clinical Genome Resource (ClinGen) has created the ClinVar database of
clinically annotated genomic variation that concentrates the knowledge and curation capabilities
of our clinical laboratory community into a public environment. Sharing data from the large
number of clinical genetic tests being performed on patients with disease phenotypes presents a
unique opportunity to contribute to our understanding of the functional significance of human
genomic variation, which will benefit the growing community of medical genomics clinicians
and researchers.
The investigators at LAB NAME HERE will focus on collecting and sharing information on
genomic variants identified through clinical genetic testing in the LAB NAME HERE laboratory.
The specific objectives of the ClinGen project are:
1) Coordinate the submission of aggregate variant data from LAB NAME HERE into ClinVar, a
unified database at NCBI.
2) Implement sustainable expert clinical level curation systems for human genomic variants.
Study Population
Patients who have had clinical genetic testing through LAB NAME HERE. This includes
patients with genetic disorders as well as patients with somatic cancer and patients with a family
history or other risk for disease (edit this section as appropriate for your laboratory).
Data To Be Collected / Obtained (edit this section as appropriate for your laboratory)
Administrative:
 Coded encounter data (diagnoses, procedures, dates)
 Demographic data (age, gender, vital status)
 Personal data (name, address, PCP)
Health / Medical:
 History / Physical
 Problem List
Health/Medical Reports/Results:
 Laboratory
 Pathology reports (reports only).
 Radiology
Other Health/Medical Information:
 Clinical genetic testing results
Protected (Identifiable) Health Information
PHI refers to health/medical information that is accompanied by any of the listed 18 HIPAA
identifiers or by a code where the key to the code that links to the identifiers is accessible to
investigators. DE-IDENTIFIED DATA (without any identifiers or codes that link back to
individuals) are not considered PHI, and are not subject to HIPAA regulations.
Will you be recording any of the identifiers listed above with the data or using a code to link the
data to any of the identifiers? If yes, than under the HIPAA Privacy Rule provisons the data
cannot be considered de-identified and authorization from the subject or a waiver of
authorization must be granted by the IRB.
When answering this question, consider the need for recording dates or retaining direct
identifiers, such as name and/or medical record number, to link data from multiple sources, to
avoid duplicating records, or for QA purposes. NOTE: If you are recording medical record
number or other identifiers, even if temporarily for QA purposes or to avoid duplicating records,
then answer "Yes".
Check the identifiers that will be recorded with or linked by code to the data (edit this section as
appropriate for your laboratory).
 Name
 Medical record number
 Dates (except year), e.g., date of birth; admission / discharge date; date of procedure; date
of death
 Other identifier; or combination of identifiers likely to identify the subject will be
recorded: Lab accession number and family number
Explain why it would be impossible to conduct the research without access to and use of
identifiable health / medical information.
Because LAB NAME HERE is a clinical laboratory, it must maintain PHI. However, no PHI
will be submitted to NCBI.
Explain why identifiers must be retained indefinitely, for example, for a health or research
purpose, legal or institutional requirement, or other reason. Be specific.
PHI must be maintained as this data is also used for clinical care and must therefore be retained
according to CLIA guidelines.
Waiver of Informed Consent / Authorization
The risks for this project involve the release of identifiable clinical or genotype data. Multiple
protections are built into the program to reduce this risk. The investigators recognize that rights
and privacy of subjects who participate must be protected at all times. Therefore, care will be
taken to ensure that data submitted to NCBI will be free of identifiers that would permit linkages
to individual subjects and free of data elements that could lead to disclosure of individual
subjects. Language will be added to LAB NAME HERE requisition form to notify patients and
providers that deidentified information may be shared with other clinical laboratories.
Data from LAB NAME HERE submitted to NCBI's ClinVar will consist of only variant-level
data, including variants and their annotations with evidence aggregated across one or more
individuals. LAB NAME HERE will create unique IDs for the variants. Variant IDs are
important for enabling data to be updated over time in ClinVar. Variant IDs are separate from the
lab accession IDs (which will not be shared with ClinVar). The data elements of ClinVar are
stored using reliable, standard technologies, including a relational database in order to ensure
transactional integrity, backup, transaction history and rollback, and custodianship. Deidentified, coded data will be securely transferred to the databases at NCBI under appropriate
data security protocols.
Re-contacting patients to obtain formal consent is not possible for most clinical laboratories and
not feasible for the scope of this project. Often, patient contact information is not provided to
clinical testing laboratories, making it impossible to contact patients directly.
Multiple measures are in place to protect the privacy of individuals' and their health information.
Data shared with ClinVar will be aggregate variant-level data. The following Privacy Safeguards
will be in place for all publicly shared aggregate variant-level data in NCBI's ClinVar:
1) All data samples will include the name of the testing laboratory and a laboratory provided
variant code. This code will not be displayed with the data, a separate ClinVar ID will be
publically displayed with the variant.
2) No personal health identifiers for the tested individuals or information regarding the
ordering physicians will be included in the data submission.
3) NCBI will never be provided with the keys to the codes.
Research Data
Electronic Research Data (edit this section as appropriate for your laboratory)
The desktop computers that the research data will be stored and accessed on are located in the
LAB NAME HERE offices.
ClinVar is a separate entity and is maintained by NCBI.
Study staff who are members of LAB NAME HERE will have access to the research data. These
study staff members are part of the LAB NAME HERE staff and are involved in the routine
operations of clinical genetic testing and support for the interpretation of test results. Their
access to the data will follow the protocols of the clinical testing laboratory.
Those not working directly with LAB NAME HERE will not have access to identifiable
information, but rather access to the larger data set of aggregate variant-level data available to
the public through ClinVar.
Sending Health / Medical Information to Collaborators Outside LAB NAME HERE
No data with direct identifiers will be shared outside LAB NAME HERE.
Aggregate variant-level data (listed on the "Aggregate variant-level data fields" form, attached)
will be sent outside LAB NAME HERE to NCBI but will not contain health or medical
information on any one individual.
Only aggregate variant-level data will be sent outside LAB NAME HERE, to NCBI for the
ClinVar database.