Harboring of Unexpected Genetic VariantNCT03632239
Reverse Phenotyping Core
An observational study of Harboring of Unexpected Genetic Variant, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
Trial summary
Background: Genes tell a person's body how to grow and work. All people have variations in their genes. Some of these cause differences that show up in a person's traits or their health, others do not. Researchers want to gather more data on people based on their genes. Read more about this study
- Who is it for?
- Ages 4 to 120 years
- Conditions the study is for
- Harboring of Unexpected Genetic Variant
- How many people
- 1,000 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Jan 2020to 29 Dec 2099
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 120 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Individuals who have undergone genome sequencing under separate protocol
Who may be able to join
- Participants in the RPC Genomic Data Archive must have exome or genome sequencing available that collaborators have permission to share for inclusion in our resource.
- Participants in the RPC Genomic Data Archive must be re-contactable by the primary study team (e.g., the collaborator who contributes their data must be able to contact the participants).
- All participants must be >= 4 years old.
- Health Perceptions Survey Criterion: Only adult participants who are able to provide consent for themselves will be eligible for this portion of the study.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Reverse Phenotyping Core (RPC)
Background:
Genes tell a person's body how to grow and work. All people have variations in their genes. Some of these cause differences that show up in a person's traits or their health, others do not. Researchers want to gather more data on people based on their genes. They want to use this data to learn more about diseases and possible treatments.
Read more
Objectives:
To develop a cohort of participants who can be contacted again for phenotyping and collect their genetic data. To share those data with other researchers and make them searchable.
Eligibility:
People already enrolled in a wide variety of protocols. They will be of varying health status, age, and sex. They will have had or plan to have exome or genome sequencing under their protocol. They can be re-contacted by the research team for possible other studies.
Design:
Participants will give basic details like contact and demographic information.
Participants may answer questions about their personal health history, their family medical history, or their thoughts or reactions to data.
Participants may have basic health tests. Their height, weight, or blood pressure may be checked.
Participants may have tests of heart function. They may have an ultrasound or other non-invasive test.
Participants may provide blood, urine, or other samples.
Participants may have scans or other tests.
Participants will get the results of all clinical tests in a letter.
If any tests are abnormal, someone from the study will call the participant to explain what the results mean and what to do about them.
Participants will get genetic testing results only if researchers think they could affect the health of the participant or their relatives.
Read the detailed description
Study Design:
RPC will be a data resource of genetic variants with the capability of performing phenotyping for selected study participants who have undergone genome or exome sequencing and were consented for data sharing and re-contact. De-identified genome or exome data will be collected as the RPC Genomic Data Archive and available in a web browser quantifying alleles in aggregate. Investigators may request additional data for research on the basis of variants of interest identified in the browser. Individuals with genetic variants of interest may be offered phenotyping under RPC. Phenotyping performed under RPC will include obtaining medical information, gathering biologic samples, and selected diagnostic studies that can be performed in the NIHCC (NIH Clinical Center). RPC will enable investigation of phenotypic consequences of genetic variation in humans by using a genomic ascertainment strategy to minimize the bias of phenotypic ascertainment.
Primary Objective:
- To pilot the development of a cohort of individuals with genome or exome sequencing data who can be re-contacted for phenotyping and make those data available to and searchable by collaborators.
- To facilitate the completion of genotype-driven research projects by RPC or other investigators.
Secondary Objectives:
Secondary objectives will relate to the studies that will address phenotypic consequences of specific genetic variants identified in the RPC cohort. Such studies will include investigation of the phenotypic spectrum associated with genetic variation.
Endpoints:
This is a hypothesis-generating research study and therefore has no concrete endpoints.
- Conditions
- Harboring of Unexpected Genetic Variant
- Keywords
- Resource, Variant, Sequencing, Genome, Phenotype, Natural History
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Reverse Phenotyping Core | Individuals undergoing phenotyping by the Reverse Phenotyping Core (RPC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hypotheses from RPC to be tested
RPC will generate data regarding phenotypic consequences of genetic variants
Measured: yearly
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2018
- Study start23 Jan 2020
- Primary completion1 Jun 2099 (estimated)
- Study completion29 Dec 2099 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Harboring of Unexpected Genetic VariantStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Human Genome Research Institute (NHGRI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Clesson E Turner, M.D., Principal investigator, National Human Genome Research Institute (NHGRI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03632239
- Sponsor's protocol ID
- 180129
- Other IDs
- 18-HG-0129
- Status last verified
- 22 Sep 2026
- First submitted
- 14 Aug 2018
- Last updated
- 16 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: We are actively depositing data into the database of genotypes and phenotypes (dbGaP), which is designed with tiered access to clinical data. That is, there is open, public access to summary clinical data of study participants and qualified investigators may apply for access to individual, coded clinical results. Such access is limited to authorized medical researchers and redistribution and security policies are strict. Broad future use of the data deposited into dbGaP (as opposed to restricted use for specific disorders) will be permitted. Sequence traces for individual genes will be available publicly (deposited in GenBank); however, these sequence traces will not be linked to a participant's identifiable information, nor to the sequence traces of other genes sequenced in that participant's sample. Coded genomic data are available to data contributors and NIH intramural investigators through the Reverse Phenotyping Core browser (18-HG-0129; https://rpc.nhgri.nih.gov/).
Publications
Wilczewski CM, Obasohan J, Paschall JE, Zhang S, Singh S, Maxwell GL, Similuk M, Wolfsberg TG, Turner C, Biesecker LG, Katz AE. Genotype first: Clinical genomics research through a reverse phenotyping approach. Am J Hum Genet. 2023 Jan 5;110(1):3-12. doi: 10.1016/j.ajhg.2022.12.004.
PubMed 36608682Garnai SJ, Brinkmeier ML, Emery B, Aleman TS, Pyle LC, Veleva-Rotse B, Sisk RA, Rozsa FW, Ozel AB, Li JZ, Moroi SE, Archer SM, Lin CM, Sheskey S, Wiinikka-Buesser L, Eadie J, Urquhart JE, Black GCM, Othman MI, Boehnke M, Sullivan SA, Skuta GL, Pawar HS, Katz AE, Huryn LA, Hufnagel RB; Genomic Ascertainment Cohort; Camper SA, Richards JE, Prasov L. Variants in myelin regulatory factor (MYRF) cause autosomal dominant and syndromic nanophthalmos in humans and retinal degeneration in mice. PLoS Genet. 2019 May 2;15(5):e1008130. doi: 10.1371/journal.pgen.1008130. eCollection 2019 May.
PubMed 31048900Manthiram K, Preite S, Dedeoglu F, Demir S, Ozen S, Edwards KM, Lapidus S, Katz AE; Genomic Ascertainment Cohort; Feder HM Jr, Lawton M, Licameli GR, Wright PF, Le J, Barron KS, Ombrello AK, Barham B, Romeo T, Jones A, Srinivasalu H, Mudd PA, DeBiasi RL, Gul A, Marshall GS, Jones OY, Chandrasekharappa SC, Stepanovskiy Y, Ferguson PJ, Schwartzberg PL, Remmers EF, Kastner DL. Common genetic susceptibility loci link PFAPA syndrome, Behcet's disease, and recurrent aphthous stomatitis. Proc Natl Acad Sci U S A. 2020 Jun 23;117(25):14405-14411. doi: 10.1073/pnas.2002051117. Epub 2020 Jun 9.
PubMed 32518111Johnston JJ, Brennan ML, Radenbaugh B, Yoo SJ, Hernandez SM; NHGRI Reverse Phenotyping Core; Lewis KL, Katz AE, Manolio TA, Biesecker LG. The ACMG SF v3.0 gene list increases returnable variant detection by 22% when compared with v2.0 in the ClinSeq cohort. Genet Med. 2022 Mar;24(3):736-743. doi: 10.1016/j.gim.2021.11.012. Epub 2021 Nov 18.
PubMed 34906458Spontarelli K, Young VC, Sweazey R, Padro A, Lee J, Bueso T, Hernandez RM, Kim J, Katz A, Rossignol F, Turner C, Wilczewski CM, Maxwell GL, Holmgren M, Bailoo JD, Yano ST, Artigas P. ATP1A1-linked diseases require a malfunctioning protein product from one allele. Biochim Biophys Acta Mol Cell Res. 2024 Jan;1871(1):119572. doi: 10.1016/j.bbamcr.2023.119572. Epub 2023 Sep 1.
PubMed 37659504
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reverse Phenotyping Core (RPC)
- ClinicalTrials.gov ID
- NCT03632239
- Acronym / sponsor ID
- 180129
- Conditions
- Harboring of Unexpected Genetic Variant
- Keywords
- Resource, Variant, Sequencing, Genome, Phenotype, Natural History
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- National Human Genome Research Institute (NHGRI)US National Institutes of Health
- Study start
- 23 Jan 2020 (actual)
- Primary completion
- 1 Jun 2099 (estimated)
- Study completion
- 29 Dec 2099 (estimated)
- First posted
- 15 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Genes tell a person's body how to grow and work. All people have variations in their genes. Some of these cause differences that show up in a person's traits or their health, others do not. Researchers want to gather more data on people based on their genes. They want to use this data to learn more about diseases and possible treatments.
Objectives:
To develop a cohort of participants who can be contacted again for phenotyping and collect their genetic data. To share those data with other researchers and make them searchable.
Eligibility:
People already enrolled in a wide variety of protocols. They will be of varying health status, age, and sex. They will have had or plan to have exome or genome sequencing under their protocol. They can be re-contacted by the research team for possible other studies.
Design:
Participants will give basic details like contact and demographic information.
Participants may answer questions about their personal health history, their family medical history, or their thoughts or reactions to data.
Participants may have basic health tests. Their height, weight, or blood pressure may be checked.
Participants may have tests of heart function. They may have an ultrasound or other non-invasive test.
Participants may provide blood, urine, or other samples.
Participants may have scans or other tests.
Participants will get the results of all clinical tests in a letter.
If any tests are abnormal, someone from the study will call the participant to explain what the results mean and what to do about them.
Participants will get genetic testing results only if researchers think they could affect the health of the participant or their relatives.
Detailed description
Study Design:
RPC will be a data resource of genetic variants with the capability of performing phenotyping for selected study participants who have undergone genome or exome sequencing and were consented for data sharing and re-contact. De-identified genome or exome data will be collected as the RPC Genomic Data Archive and available in a web browser quantifying alleles in aggregate. Investigators may request additional data for research on the basis of variants of interest identified in the browser. Individuals with genetic variants of interest may be offered phenotyping under RPC. Phenotyping performed under RPC will include obtaining medical information, gathering biologic samples, and selected diagnostic studies that can be performed in the NIHCC (NIH Clinical Center). RPC will enable investigation of phenotypic consequences of genetic variation in humans by using a genomic ascertainment strategy to minimize the bias of phenotypic ascertainment.
Primary Objective:
- To pilot the development of a cohort of individuals with genome or exome sequencing data who can be re-contacted for phenotyping and make those data available to and searchable by collaborators.
- To facilitate the completion of genotype-driven research projects by RPC or other investigators.
Secondary Objectives:
Secondary objectives will relate to the studies that will address phenotypic consequences of specific genetic variants identified in the RPC cohort. Such studies will include investigation of the phenotypic spectrum associated with genetic variation.
Endpoints:
This is a hypothesis-generating research study and therefore has no concrete endpoints.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Reverse Phenotyping Core | – | –Individuals undergoing phenotyping by the Reverse Phenotyping Core (RPC) |
Who may qualify
- Ages
- 4 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Individuals who have undergone genome sequencing under separate protocol
Key inclusion criteria (4 listed)
- Participants in the RPC Genomic Data Archive must have exome or genome sequencing available that collaborators have permission to share for inclusion in our resource.
- Participants in the RPC Genomic Data Archive must be re-contactable by the primary study team (e.g., the collaborator who contributes their data must be able to contact the participants).
- All participants must be >= 4 years old.
- Health Perceptions Survey Criterion: Only adult participants who are able to provide consent for themselves will be eligible for this portion of the study.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Hypotheses from RPC to be tested
Time frame: yearly
RPC will generate data regarding phenotypic consequences of genetic variants
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2026.
- Background: PubMed 36608682Wilczewski CM, Obasohan J, Paschall JE, Zhang S, Singh S, Maxwell GL, Similuk M, Wolfsberg TG, Turner C, Biesecker LG, Katz AE. Genotype first: Clinical genomics research through a reverse phenotyping approach. Am J Hum Genet. 2023 Jan 5;110(1):3-12. doi: 10.1016/j.ajhg.2022.12.004.
- Background: PubMed 31048900Garnai SJ, Brinkmeier ML, Emery B, Aleman TS, Pyle LC, Veleva-Rotse B, Sisk RA, Rozsa FW, Ozel AB, Li JZ, Moroi SE, Archer SM, Lin CM, Sheskey S, Wiinikka-Buesser L, Eadie J, Urquhart JE, Black GCM, Othman MI, Boehnke M, Sullivan SA, Skuta GL, Pawar HS, Katz AE, Huryn LA, Hufnagel RB; Genomic Ascertainment Cohort; Camper SA, Richards JE, Prasov L. Variants in myelin regulatory factor (MYRF) cause autosomal dominant and syndromic nanophthalmos in humans and retinal degeneration in mice. PLoS Genet. 2019 May 2;15(5):e1008130. doi: 10.1371/journal.pgen.1008130. eCollection 2019 May.
- Background: PubMed 32518111Manthiram K, Preite S, Dedeoglu F, Demir S, Ozen S, Edwards KM, Lapidus S, Katz AE; Genomic Ascertainment Cohort; Feder HM Jr, Lawton M, Licameli GR, Wright PF, Le J, Barron KS, Ombrello AK, Barham B, Romeo T, Jones A, Srinivasalu H, Mudd PA, DeBiasi RL, Gul A, Marshall GS, Jones OY, Chandrasekharappa SC, Stepanovskiy Y, Ferguson PJ, Schwartzberg PL, Remmers EF, Kastner DL. Common genetic susceptibility loci link PFAPA syndrome, Behcet's disease, and recurrent aphthous stomatitis. Proc Natl Acad Sci U S A. 2020 Jun 23;117(25):14405-14411. doi: 10.1073/pnas.2002051117. Epub 2020 Jun 9.
- Background: PubMed 34906458Johnston JJ, Brennan ML, Radenbaugh B, Yoo SJ, Hernandez SM; NHGRI Reverse Phenotyping Core; Lewis KL, Katz AE, Manolio TA, Biesecker LG. The ACMG SF v3.0 gene list increases returnable variant detection by 22% when compared with v2.0 in the ClinSeq cohort. Genet Med. 2022 Mar;24(3):736-743. doi: 10.1016/j.gim.2021.11.012. Epub 2021 Nov 18.
- Background: PubMed 37659504Spontarelli K, Young VC, Sweazey R, Padro A, Lee J, Bueso T, Hernandez RM, Kim J, Katz A, Rossignol F, Turner C, Wilczewski CM, Maxwell GL, Holmgren M, Bailoo JD, Yano ST, Artigas P. ATP1A1-linked diseases require a malfunctioning protein product from one allele. Biochim Biophys Acta Mol Cell Res. 2024 Jan;1871(1):119572. doi: 10.1016/j.bbamcr.2023.119572. Epub 2023 Sep 1.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. We are actively depositing data into the database of genotypes and phenotypes (dbGaP), which is designed with tiered access to clinical data. That is, there is open, public access to summary clinical data of study participants and qualified investigators may apply for access to individual, coded clinical results. Such access is limited to authorized medical researchers and redistribution and security policies are strict. Broad future use of the data deposited into dbGaP (as opposed to restricted use for specific disorders) will be permitted. Sequence traces for individual genes will be available publicly (deposited in GenBank); however, these sequence traces will not be linked to a participant's identifiable information, nor to the sequence traces of other genes sequenced in that participant's sample. Coded genomic data are available to data contributors and NIH intramural investigators through the Reverse Phenotyping Core browser (18-HG-0129; https://rpc.nhgri.nih.gov/).
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Clesson E Turner, M.D. principal investigator
National Human Genome Research Institute (NHGRI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Harboring of Unexpected Genetic Variant, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hypotheses from RPC to be tested (time frame: yearly). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03632239, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2026.