GCI Curation Help
This was the curation help for the retired 1.0 GCI/VCI platform. To see the Help doc for the current 2.0 platform, go to: Curation Help for GCI
REGISTRATION
LOGGING IN TO THE CURATION INTERFACES
OVERVIEW OF CURATION
AFFILIATIONS
GENERAL NAVIGATION
CREATING A GENE DISEASE RECORD
- Identifying the Gene
- Identifying the Disease
- Identifying the Mode of Inheritance
- Free text option for disease
- Selecting an Adjective (optional)
STARTING CURATION
ADDING GENETIC EVIDENCE
- Curate Group Information
- Curate Family Information
- Curate Individual Information
- Curate Case Control Information
ADDING EXPERIMENTAL EVIDENCE
CLASSIFICATION MATRIX
SAVING & MODIFYING A SUMMARY CLASSIFICATION
EVIDENCE SUMMARY
SAVING AS PROVISIONAL AND APPROVED
- What do Provisional and Approved mean?
- Saving as Provisional
- Saving as Approved
- Creating New Provisional and Approved Classifications
PUBLISHING APPROVED CLASSIFICATIONS TO THE CLINGEN WEBSITE
ClinGen curators who would like to access the production version of the ClinGen curation interfaces (https://curation.clinicalgenome.org/) will need to register for production interface (see section 2, below, on how to register). Data entered into the production interface is permanently saved, so this interface should only be used for “real” curation.
We recommend curators become familiar with the curation interfaces by exploring the test interface ((https://curation-test.clinicalgenome.org/)) before curating “real” evidence into the production interface. Data entered into the test interfaces is erased several times per year and so do NOT enter any data you wish to be permanently saved.
i. If you are a ClinGen curator, you may request an account by emailing us at clingen-helpdesk@lists.stanford.edu. The ClinGen Variant Curation Interface is available for public use. However, the ClinGen Gene Curation Interface is currently restricted to use by ClinGen curators. If you would like to collaborate on gene curation, please contact ClinGen at clingen@clinicalgenome.org.
ii. When you write to us please let us know the following:
a. Your preferred email address (which you will use to log in to the interfaces)
b. Your preferred display name (first and last name)
c. Any affiliation you have with ClinGen
iii. We will write back to you to confirm that your email address has been registered and can be used for logging in to the interfaces.
Upcoming: In mid-December 2020 we will launch a newly rearchitected VCI/GCI platform known as the 2.0 site. If you had a VCI/GCI login before December 2020 your account will be transferred along with all of your curation data and affiliations.
To access your curations within the new platform please do the following:
- Navigate to: https://curation.clinicalgenome.org/
- Click “login” in the upper right corner
- Enter your VCI/GCI registered email as “Username”
- Enter any text into the password field - it does not need to be your current VCI/GCI password
- You’ll be re-directed to the “Reset your password” modal
- Click on “Resend Code”
- Check your email for the sent code
- Enter code and choose a password You should now have access to the site and see all of your affiliations and curations.
If you're having issues accessing the new site please try the following:
- If you don't see the verification code:
- Ensure you are using the registered email to sign up.
- Check your spam email folder if you don't receive an email with a code within about 15 minutes of clicking on the "resend code" button. The email containing the code will be titled "Your verification code" and be sent from the email address domain "@verificationemail.com"
- If you logged in but can't see any content:
- Do a hard refresh on your browser (google how to do this for the browser you are using).
- If you are still having issues please contact us at clingen-helpdesk@lists.stanford.edu.
An Affiliation is any set of people collectively represented in ClinGen resources (e.g. ClinGen Working Groups, ClinGen Expert Panels, Research Labs, Clinical Labs, etc.) that are specified to:
- Edit and score/evaluate same piece of evidence
- Work on same classification/interpretation
- Approve the same classification/interpretation
If a user is not part of any Affiliations then there will be no difference from their current workflow. All actions they take in the interfaces will be attributed to them alone.
If a user is as a member of at least one Affiliation, then after logging in they will be presented with a modal.
Within the pulldown the user can choose to select 'No Affiliation (User Name)', in which case they can continue to the interfaces with no difference from their current workflow, or they can select one of the Affiliations they are a member of from the list and all actions taken within the interfaces will be attributed to the selected Affiliation.
Once an Affiliation has been selected then a dark blue Affiliation banner will appear beneath the header, which will show the Affiliation name. This Affiliation banner will be present on every page during the session.
On the dashboard page a user can change Affiliation at any time by clicking on the 'Change Affiliation' button in the Affiliation banner. The Affiliation pop-up modal will re-appear and a new Affiliation can be selected from the pulldown.
On other pages within the interfaces there is a helpful 'home' button link within the Affiliation banner that will take you back to the dashboard. Once back on the dashboard page, a user can change Affiliation by clicking on the 'Change Affiliation' button in the Affiliation banner and proceed as above.
To request to set up a new Affiliation the Coordinator should email the help-desk at clingen-helpdesk@lists.stanford.edu, and provide the following information:
- Name of the Affiliation
- Name of the Coordinator
- Email address of the Coordinator
- Names of all members of the Affiliation
- Email addresses of all members of the Affiliation (these should be the email addresses used in their interface registration)
- Names of the Approver(s) for the Affiliation (if no Approver(s) are selected then by default all Approvals will be by the Affiliation with no Approver shown)
- Email addresses of the Approver(s)
- Whether the Affiliation will need to submit Interpretations/Classifications to the ClinGen website (clinicalgenome.org)
All management of the Affiliation should be done by the Coordinator. Including:
- Making sure all members are registered to use the interfaces
- Making sure all members are trained in the demo interface before entering data into the production database
- Making sure all information about the Affiliation is up-to-date
NOTE: All communication about updating an Affiliation must come via the Coordinator (e.g. new members, removing members, changing the name of the Affiliation, etc.)
a Dashboard home – available from all pages
b Navigating to “Select Variant for Variant Curation” – available from all pages
c Navigating to “Create Gene-Disease Record” (described below) – available from all pages d Navigating to the online Help documentation – available from all pages
e Navigating to “Select Variant for Variant Curation”
f View a list of all Variant Interpretations – This list contains all the Interpretations curated to date, along with their status, creator, date created and date last edited.
g Navigating to “Create Gene-Disease Record” (described below)
h View a list of all Gene-Disease Records – This list contains all the Gene-Disease Records curated to date, along with their status, creator, date created and date last edited.
i View of a curator’s recent history – This section provides a chronological history of all edits made by a curator within both the Gene and Variant Curation Interfaces. A curator only views their own history. Each highlighted text is a direct link to the relevant section of the Gene or Variant Curation Interface a curator was previously curating.
j View of a curator’s current Variant Interpretation curation records – This section provides a list of edits made by a curator within the Variant Curation Interface. A curator only views their own Interpretations. Each highlighted text is a direct link to the variant a curator was previously curating.
k View of a curator’s current Gene-Disease curation records – This section provides a list of edits made by a curator within the Gene Curation Interface. A curator only views their own Gene-Disease Records. Each highlighted text is a direct link to the Gene-Disease Record a curator was previously curating.
m. Logout – available from all pages
NOTE: Currently, once a Gene:Disease Record has been created, the disease can be altered up until a PMID has been added. However, the gene, mode of inheritance, and adjective cannot be altered after the record has been created. Please be certain you have selected the desired fields correctly from the beginning.
A curator is required to identify the specific gene by entering an approved HGNC gene symbol. A link out to HGNC is provided for a curator to look up the correct symbol for their gene.
A curator is required to identify the specific disease by entering an MonDO ID. Click on the “Disease +” button to add a disease For additional help in searching for MonDO IDs, please see the “MonDO Search Help” link (https://curation.clinicalgenome.org/static/help/MonDO-search-help.pdf) for further instructions.
After entering an ID and selecting “Retrieve from OLS,” the term name and definition (if one exists) will be returned. Select “Save” if this is the desired term.
After entering an ID and saving, the disease term name, ID, and definition (if one exists) will be displayed on the Create GDM page:
A curator is required to identify the specific Mode of Inheritance by choosing from the selection available in the pull-down.
If there is no MonDO term, a free text term may be entered for the disease. Note: using a disease identifier if highly recommended. If you cannot find an appropriate one, please feel free to contact us at clingen-helpdesk@lists.stanford.edu and we will be happy to assist.
To enter a free text term, verify you click on the checkbox (see arrow below)
This will take you to a page where you can enter a free text term (up to 100 characters in length). You must also provide either a set of HPO terms (preferred) or a Definition for the term you are entering. You may also provide both. Please remember that if someone else enters a different phrase for the same ID, the interface will not be able to determine they are equivalent.
A curator can add an adjective to the Mode of Inheritance by choosing from the selection available in the pull-down.
NOTE: Currently, once a Gene:Disease Record has been created, the disease can be altered up until a PMID has been added. However, the gene, mode of inheritance, and adjective cannot be altered after the record has been created. Please be certain you have selected the desired fields correctly from the beginning.
This is the landing page/homepage for each Gene-Disease curation.
a. First line of header shows the Gene Symbol and Disease selected by a curator.
b. Second line of header shows the Mode of Inheritance selected by a curator. If a curator selected an adjective then this will appear in parentheses.
c. Curation Central home – available from all pages.
d. History of the last saved Summary and any Provisional Classifications for the Gene-Disease record.
e. View Classification Matrix – available from all pages.
f. Gene symbol and links to HGNC and NCBI Gene.
g. Disease name and links to disease term and OMIM.
h. The name of the curator who first created the Gene-Disease record and the timestamp of when they did so.
i. List of all participants who have made edits to the Gene-Disease record.
j. Curator name and timestamp for the most recent edit to the Gene-Disease record.
i. To add a PubMed article to the Gene-Disease record click the “Add New PMID” button .
ii. Enter the PMID into the modal that appears and click the “Retrieve PubMed Article” button.
iii. Based on the PMID entered the authors, title, and citation details will be auto-filled. If these details are correct then a curator can add that PMID to the Gene-Disease Record by clicking the “Add Article” button.
iv. The PMID has now been added to the Curation Central view for that Gene-Disease Record.
a. All articles that have been added to the record can be found in a scrollable panel on the left-hand side, with the first author, title, citation details, and PMID shown for each article. By default a newly added article will be the one selected for curation in the interface, as shown by a blue border. To select an alternative article for curation, a curator simply needs to click on that article in the left-hand panel.
b. The central panel shows more details about the article selected by a curator, including all authors, the title, a link to PubMed, and the full abstract.
c. An evidence curation palette on the right-hand side provides now provides access to curation resources for adding Genetic and Experimental Evidence found in the selected article.
d. Further articles can be added to the Gene-Disease Record by clicking the “Add New PMID” button.
The gene curation palette on the right-hand side is the starting point for adding evidence for a selected article. To begin curation a curator clicks the ‘+’ sign next to specific type of evidence they wish to curate.
The top of the landing page to Curate Group Information shows the authors, title, and citation details for the selected PubMed article in a yellow box below the header. A curator is required to enter a label for the Group, if possible using a label described in the paper.
The rest of the Curate Group Information page is split into relevant sections based on the type of evidence:
i. Group – Common Disease(s) & Phenotype(s)
A curator is required to enter at least one of the following to describe disease(s)/phenotype(s) common to the group:
a) MonDO ID (or free text)
b) HPO ID(s)
c) Phenotype free text
ii. Group – Demographics
Enter information about the demographics of the group.
iii. Group – Information
Enter information about the individuals in the group. A curator is required to enter the total number of individuals in the group.
iv. Group – Methods
Enter information about the methods used to obtain genetic data for the Group.
v. Group – Additional Information
Enter any additional information about the Group.
vi. Cancel/Save buttons
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Clicking the “Cancel” button, found at the bottom of the Curate Group Information page, will return a curator to the Record Curation page without saving any entered data.
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Clicking the “Save” button, found at the bottom of the Curate Group Information page, is the only way to save all the Group data added by a curator. Navigating away from this page without saving will result in the loss of any entered data.
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After clicking the “Save” button if any of the required fields (described above) are not filled in, then a red text warning will appear next to the buttons.
- Additionally, a red text warning will appear next to the required fields that need to be curated before the page can be saved.
If the Family to be entered is part of a Group already curated in this Gene-Disease Record then it can be added when prompted after saving a Group by selecting ‘Yes’ from the pull-down, and then ‘Add New Family for this Group’:
It can also be added directly from that Group in the curation palette on the Record page.
To add a new Family that is not associated with a Group, click the Family ‘+’ in the curation palette.
The top of the landing page to Curate Family Information shows the authors, title, and citation details for the selected PubMed article in a yellow box below the header. A curator is required to enter a label for the Family, if possible using a label described in the paper.
The rest of the Curate Family Information page is split into relevant sections based on the type of evidence. The first three sections are in a similar format to the same sections in the Curate Group Information:
i. Family – Disease(s) & Phenotype(s)
ii. Family – Demographics
iii. Family – Methods
iv. Family – Segregation. This section is split into two separate sections for adding information on tested individuals and LOD score respectively.
Fields for entering information on Tested Individuals within a Family:
a) For a Dominant and Recessive disease/phenotype a curator is required to enter the total number of AFFECTED individuals in the Family WITH the genotype for that disease/phenotype.
b) For a Recessive disease/phenotype a curator is required to enter the total number of UNAFFECTED individuals in the Family WITHOUT the biallelic genotype for that disease/phenotype.
c) Enter the total number of segregations reported for the Family.
d) If there are any inconsistent segregations amongst the TESTED Individuals then ‘Yes’ should be selected from the pull-down. If not, then select ‘No’.
e) If ‘Yes’ is selected in the prior field then optional free text can be added here to describe the inconsistent segregations.
f) If the Family is consanguineous then ‘Yes’ should be selected from the pull-down. If not, then select ‘No’. If this is unknown then selected ‘Not Specified’.
g) If a pedigree was provided in the publication, then optional free text can be added here to describe the location of the pedigree within the paper.
For entering information on a LOD Score for the Family, there are two separate scenarios based on whether the LOD score was published in the paper or not.
Published LOD Score
If the entered published LOD score should be included in the final aggregate calculation then ‘Yes’ must be selected from the pull-down. If the entered published LOD score should NOT be included in the final aggregate calculation then ‘NO’ should be selected from the pull-down.
A box is provided to add free text to ‘Explain reasoning’ behind this decision. A further free text box allows ‘Additional Segregation Information’ to be entered.
Estimated LOD Score
If there is no Published LOD Score then Select ‘No’ from the pull-down. If the required Tested Individual fields (above) have been entered then the Estimated LOD score will be calculated automatically within the interface.
If the estimated LOD score should be included in the final aggregate calculation then ‘Yes’ must be selected from the pull-down.
If the estimated LOD score should NOT be included in the final aggregate calculation then ‘NO’ should be selected from the pull-down.
A box is provided to add free text to ‘Explain reasoning’ behind this decision. A further free text box allows ‘Additional Segregation Information’ to be entered.
v. Family – Variant(s) Segregating with Proband
To score the proband for a Family then, in addition to the LOD score for the segregation, an Individual proband will need to be created including adding their associated variant(s).
a. A curator is required to enter a label for the Proband, if possible using a label described in the paper. A real name should not be entered.
b. The disease ID(s) for the disease(s) associated with the Family automatically shown.
c. Enter the disease ID(s) for the disease(s) associated with the Individual.
d. Click this button to automatically copy the disease ID(s) for the disease(s) associated with the Family to the field above for the Individual.
e. Check this box if the Individual is homozygous.
f. Check this box if the Individual is hemizygous.
g. Click this button to add the first variant associated with the Individual via a ClinVar ID.
h. Click this button to add the first variant associated with the Individual via a ClinGen Allele Registry CA ID.
i. Click this button to add a second variant (where appropriate) associated with the Individual via a ClinVar ID.
j. Click this button to add a second variant (where appropriate) associated with the Individual via a ClinGen Allele Registry CA ID.
Adding Variants
When adding a Variant associated with an Individual via the ‘Add ClinVar ID’ or ‘Add CA ID’ buttons, a pop-up window will appear. Enter the ClinVar ID or CA ID into the window and click the ‘Retrieve from ClinVar’ or ‘Retrieve from ClinGen Allele Registry’ button respectively.
Check the evidence retrieved for either the ClinVar ID or CA ID you have entered and once you are convinced the ID you have entered represents the correct variant, Select ‘Save’ to add that variant to the Individual.
The variants added via the ClinVar and/or CA IDs can now be seen associated with the Proband:
a. ClinVar Variation ID with linkout to ClinVar.
b. ClinVar Preferred Title for the variant.
c. Link within the Interface to ‘Curate Variant Information’ so that curator can enter the gene impact for that variant. (Please note: this feature was removed, but will be added back shortly.)
NOTE: A variant’s gene impact should be specified in order to score the Proband.
d. Link within the Interfaces to the ‘Evidence View’ in the Variant Curation Interface so that curator can view all known evidence (both programmatic and manually entered from papers) for that variant.
e. Clear the selected variant.
f. ClinGen Allele Registry ID with linkout to the ClinGen Allele Registry.
g. HGVS Title for the current genome build. Shown only of for novel variant that cannot be found in ClinVar and don't have an unambiguous canonical transcript that can be used.
HGVS variant titles are determined according to the following preference order:
A canonical transcript is based on the transcript with the longest translation with no stop codons OR if there’s no translation, the longest non-protein-coding transcript. If a single canonical transcript is not discernible, the HGVS is based on the GRCh38 genomic coordinates.
Once variants have been saved to a Gene Record they will appear in the Gene Record page under the header in a Gene-Disease Records Variants section. There is an individual blue box for each variant containing the name for each variant. Each box is a link to a page for curating the variant’s gene impact.
vi. Family – Cancel/Save buttons
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Clicking the “Cancel” button, found at the bottom of the Curate Family Information page, will return a curator to the Record Curation page without saving any entered data.
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Clicking the “Save” button, found at the bottom of the Curate Family Information page, is the only way to save all the Family data added by a curator. Navigating away from this page without saving will result in the loss of any entered data.
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After clicking the “Save” button if any of the required fields (described above) are not filled in, then a red text warning will appear next to the buttons.
- A red text warning will appear next to the missing required field.
A Proband Individual can be associated with a Family during the Curate Family Information process (as shown above). Upon saving the Family you can:
a. Score and/or Add information about the Proband entered with the Family (‘Scoring Probands’ discussed later)
b. Add a non-proband Individual to this Family.
c. Return to Record Curation page.
Information about Individuals can also be entered at any time from the Curation palette on the Record Curation page:
a. If the Individual to be entered is part of a Group already curated in this Gene-Disease Record then it can be added from this link within that Group.
b. If the Individual to be entered is part of a Family already curated in this Gene-Disease Record then it can be added from this link within that Family.
c. To add a new Individual that is not associated with an exiting Group or Family, click the Individual ‘+’ in the curation palette.
d. To Edit the Information already added for an existing Individual.
The top of the landing page to Curate Individual Information shows the authors, title, and citation details for the selected PubMed article in a yellow box below the header.
a. A curator is required to enter a label for the Individual, if possible using a label described in the paper. If Editing a pre-existing Individual then this Label will already be filled in but can be changed here.
b. A curator must then select ‘Yes’ if the Individual is a proband and ‘No’ if the Individual is a non-proband.
c. Selecting ‘Yes’ will make the disease field a required field.
The Curate Individual Information page is split into relevant sections based on the type of evidence:
i. Individual – Disease & Phenotype(s)
ii. Individual – Demographics
Enter information about the demographics of the group. The ‘Sex’ of an Individual is a required field; extensive options are via a pull-down.
iii. Individual – Methods
iv. Individual – Associated Variant(s)
See the section ‘Adding Variants’ above, which describes how to add Variants using either a ClinVar Variation ID(s) and/or ClinGen Allele Registry CA ID(s).
v. Individual – Additional Information
vi. Individual – Score Proband
Scoring Probands
In order to score a proband, a curator must:
a. Associate the proband with at least one variant in the ‘Individual – Associated Variant(s)’ section above.
b. Specify the gene impact for each variant associate with the proband. To do so, the curator should click on the ‘Curate variant’s gene impact’ link under the variant.
c. After following the link, a curator is required to select the gene impact for the variant from the pull-down. [Please note: this feature was removed, but will be added back shortly]
d. Each variant that has had its gene impact assessed is marked with a white box next to its variant name in the Gene-Disease Records Variants section of the Record Curation page.
e. Upon saving the gene impact for all the variants associated with a proband, you can return to the Edit Individual Information page and will now be able to Score the proband via a pull-down selection (Score, Review or Contradicts).
f. The case type must then be confirmed from the pull-down. Note: The default score and range of choice if choosing a different score will change depending on this case type choice.
g. If a curator chooses a different score from the default score then they are required to explain their reasoning in the box provided.
To add Case Control data to a record click on the ‘+’ in the curation palette on the Record Curation page.
The top of the landing page to Curate Group Information shows the authors, title, and citation details for the selected PubMed article in a yellow box below the header. A curator is required to enter a label for the Case-Control, the Case Cohort and the Control Cohort.
Upon saving the gene impact for all the variants associated with a proband, you can return to the Edit Individual Information page and will now be able to Score the proband via a pull
i. Case Cohort – Disease(s) and Phenotype(s)
A curator is required to enter at least one of the following to describe disease(s)/phenotype(s) common to the Case Cohort:
a) MonDO ID(s)
b) HPO ID(s)
c) Phenotype free text
For the following sections, there is a split screen where Case Cohort information can be entered in the left panel and Control Cohort information can be entered in the right panel.
ii. Case Cohort/ Control Cohort – Demographics
iii. Case Cohort/ Control Cohort – Methods
iv. Case Cohort/ Control Cohort – Power
v. Case Cohort/ Control Cohort – Additional Information
For instance:
Then the Case Control Evaluation section is for evaluating the evidence on the Case Control group as a whole.
vi. Case Control Evaluation – Statistics
vii. Case Control Evaluation – Bias Category
viii. Case Control Evaluation – Comments
ix. Case Control – Score
Scoring Case Control
In order to score Case Control, a curator must select a Score from the pull-down and the click Save.
To add Experimental data to a record click on the ‘+’ in the curation palette on the Record Curation page.
A curator is first required to select the Experiment Type from a pull-down:
There are six different curation experiences dependent on the Experiment Type selected by the curator.
i. Experimental – Biochemical Function (A) and (B)
The ‘Biochemical Function’ option has two separate options, A and B, provided in a pull-down.
Both have a number of required fields, shown with an asterisk next to the field. One of these required fields is for adding the Gene Ontology (GO) ID that best defines the function of the gene in the Record.
Adding GO IDs
In order to aid the curator in searching for the correct GO ID, there are 3 links provided – one to view existing GO annotations for the gene, one that links to the OLS GO Search, and one that links to Quick GO
a) Only choose either “Molecular Function” or “Biological Process”
b) Only choose manual experimental evidence, e.g. codes IDA, IMP, IGI, IPI and IEP. Other codes may be inferred, e.g. IEA which is ‘Inferred by electronic annotation’
c) As you go down a GO tree the terms become more specific, only go down the tree as far as you feel secure in your decision.
d) If you are not sure which specific GO term to add then go back up the tree until you find a general term that fits your knowledge.
Scoring Experimental Evidence
Experimental data can be scored via a pull-down selection (Score, Review or Contradicts) in Experimental Data Score sections found at the foot of every Curate Experimental Data Information page.
The default score and range of choice if choosing a different score will change depending on the experimental data type.
If a curator chooses a different score from the default score then they are required to explain their reasoning in the box provided.
ii. Experimental – Protein Interactions
Has a number of required fields, shown with an asterisk next to the field.
iii. Experimental – Expression (A and B)
The ‘Expression’ option has two separate options, A and B, provided in a pull-down.
Both have a number of required fields, shown with an asterisk next to the field. One of these required fields is for adding an anatomical structure Ontology (UBERON) ID that best defines the organ or tissue relevant to the gene expression evidence. A link out to UBERON has been provided to aid in searching for the correct ID.
iv. Experimental – Functional Alteration
Has a number of required fields, shown with an asterisk next to the field.
Includes section for adding variant(s) associated with this data type. Simply click on “Add variant associated with Experimental data’. A pop-up window will appear whereby variants can be added via either a ClinVar VariationID or a ClinGen Allele Registry CA ID.
Variants can then be added via either a ClinVar Variation ID or a ClinGen Allele Registry CA ID.
v. Experimental – Model Systems
Has a number of required fields, shown with an asterisk next to the field.
Including selecting whether it is a non-human model organism or cell culture model, and the associated ‘Description of gene alteration’.
If ‘Cell culture model’ is selected then cell culture model type/line becomes a required field. This field can accept either an Experimental Factor Ontology (EFO) ID or a Cell Ontology (CL) ID. Links out to EFO and CL ontologies within the ontology lookup service (OLS) have been provided to aid in searching for the correct ID.
Also includes section for adding variant(s) associated with this data type.
vi. Experimental – Rescue
Has a number of required fields, shown with an asterisk next to the field. For instance:
Includes section for adding variant(s) associated with this data type.
To view the Classification Matrix click on the ‘View Classification Matrix’ button found in the left upper header on each page. This will generate the Matrix for the current saved evidence and scores:
The top of the resulting page contains the Classification Matrix
- Automated upper Calculated Classification Matrix (Note: this matrix represents the saved evidence and scores at the time you clicked the “View Classification Matrix button)
For each specific evidence type there are the following columns rows (see graphic on next page to see where each item, below, is found in the matrix):
a. Evidence Type – brief description of types of evidence scored upon.
b. Count - total number of pieces of evidence scored for the Evidence Type listed
c. Total Points – the total number of points for all the pieces of evidence scored for that Evidence Type; if the maximum points allowed is reached, the number of points displayed will be the maximum value
d. Points Counted – the total of all the scores added together for each section; if the maximum points allowed is reached, the number of points displayed will be the maximum value (for each specific type of evidence there is a maximum number of points allowable, see the SOP for allowed max scores).
Each specific evidence type is shown in rows (see graphic on next page to see where each item, below, is found in the matrix):
e. Variant/proband scores, if curating an autosomal dominant disease or an X-linked disorder
f. Variant/proband scores, if curating an autosomal recessive disease.
g. Case level segregation scores
h. Case Control scores
i. Genetic Evidence Total. The total number of allowable points for genetic evidence. Calculated by adding the ‘Points Counted’ for each of the genetic evidence types NOTE: Maximum points allowed for this field is 12
j. Experimental (functional) scores
- Biochemical Functions
- Protein Interactions
- Expression
k. Experimental (functional alteration) scores
- Patient cells
- Non-patient cells
l. Experimental (model) scores
a. Non-human model organism
b. Cell culture model
m. Experimental (rescue) scores
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Rescue in human
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Rescue in non-human model organism
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Rescue in cell culture model
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Rescue in patient cells
n. Experimental Evidence Total. The total number of allowable points for experimental evidence. Calculated by adding the ‘Points Counted’ for each of the experimental evidence types
o. Total Points. The sum of the Genetic Evidence Total and Experimental Evidence Total.
For Segregation Evidence, the Total Points field additionally contains the LOD score in parentheses. If the LOD score has been generated by summing multiple LOD scores then it will have an asterisk.
NOTE: Modifying and then saving a Classification in the panel just below the Classification Matrix will NOT mark it as Provisional or Approved, but will bring up the option to save it as Provisional_.
(see graphic below to visualize where each item listed below is found on the Save Classification panel)
a. Genetic Evidence Total assigned points.
b. Experimental Evidence Total assigned points
c. Total Points
d. Replication Over Time. Tickbox to identify whether the evidence has been replicated over time. Tick for ‘Yes’, leave blank for ‘No’. (Note: this can change the Calculated Classification; to upgrade a 12-18 Total Points from a Strong to Definitive classification then ‘Yes’ must have been selected for Replication Over Time.
e. Calculated Classification is automatically filled in based on the Total Points, including your answer to “Replication Over Time?” The calculated classification is highlighted in blue.
f. Contradictory Evidence. If a Proband or Experimental evidence has been scored as Contradictory by the curator then it will have a red ‘Yes’, if not it will have a black ‘No’.
g. Curators can modify the Calculated Clinical Validity Classification by selecting an alternative Classification from the pull-down options.
h. If the curator has modified the Classification then they are required to explain their reasoning here.
i. Evidence Summary – this free text box allows curators to summarize their evidence and provide a rationale for the clinical validity.
j. Last Saved Summary Classification (i.e. Classification value saved previously, before clicking “Save”)
k. Timestamp when current Last Saved Summary Classification was saved, if previously saved
Clicking the “Save” button at the bottom of the Save Classification table will save the Classification (see above figure). The Calculated Classification will be saved by default as the Classification, unless a modification has been selected. NOTE: Saving a Classification at this step is NOT marking it as Provisional or Approved, but will bring up the option to save it as Provisional (see section below on saving as Provisional and Approved).
Upon saving the bottom of the page will be updated to a View only option to reflect the saved options. Check that everything looks correct
a. Classification value just saved (when “Save” was clicked).
b. Timestamp for the Classification value (a).
c. Link back to the Record Curation page.
d. Option to unlock the Save Classification section for re-editing (i.e. to change the modification, update the reason(s) for change text, mark as provisional, and/or update the evidence summary text).
e. View the Evidence Summary for this saved Classification for the Gene:Disease record.
Once you have saved a Summary Classification, you will see it highlighted in the header; the Classification becomes "In Progress" and a "New Saved Summary" tag appears:
With every visit to the "View Classification Matrix" page, the three editable fields in the Modify/Save Classification table are available to be edited again (i.e. you may update the modification based on any new Calculated Classification, update the reason(s) for change text, and/or update the evidence summary text). Note: The Save button must be clicked to save any edits to the current Summary Classification value.
If the new calculated Total Points now suggests a calculated Classification that is the same as a Modification saved on the last visit, then that Modification will be reset to “No Modification” and there will be a red warning message to explain this.
After saving a Classification, the option to Save it as a Provisional will appear:
Note: Please see "Saving as Provisional and Approved" Section below for information on moving a Classification to Provisional or Approved status.
Every time a curator visits the Classification Matrix (regardless as to whether a Classification has previously been saved, or saved as Provisional or Approved), all the scores in the upper Calculated Classification table are recalculated based on the current set of saved evidence and associated saved scores. You will see a yellow box below that table that explains this.
Note: Please see "Saving as Provisional and Approved" Section below for information on moving a Classification to Provisional or Approved status.
Upon saving a Classification, you have the option of viewing the summary of the evidence for this Classification by clicking on the “Evidence Summary” button at the bottom of the page. This represents the evidence and any modifications that were just saved.
The Evidence Summary will pop up as a new tab or window. Be sure to close it when you are finished. There is a close button at the top of the page as well as the bottom, just so you do not get confused the next time you generate an Evidence Summary:
The Evidence Summary table header contains a summary of information about the saved Classification:
The Evidence Summary summarizes and sorts all the evidence for the saved Classification into tables according the evidence types (Case Level, Case Level for segregation evidence when there is no associated proband, Case-Control, and Experimental). Note that evidence that is has a score status of “Score,” “Review,” or “Contradicts” is shown. For the total points shown at the bottom of each evidence table, only those rows of evidence where the score status was set as “Score” are included in the calculation.
See next page for the various tables of evidence in the Evidence Summary
Case Level Data:
Case Control Data:
Experimental Data:
When printing this view, we recommend the following print settings:
• "Landscape" for layout
• 50% for Scale
• "Minimum" for Margins
• Select "Background graphics"
You can also use your Print dialogue box to save your classification as a PDF.
The option to save as Provisional appears after saving a Summary Classification. The option to save as Approved appears after saving a Classification as Provisional.
- Provisional: Curator has marked the Classification as complete and ready for review
- Approved: Provisional Classification has been reviewed and approved by a previously designated Approver
This diagram, for reference in reviewing the sections below, illustrates the possible approval process workflows:
After saving a Classification, the option to Save it as a Provisional will appear (see bottom panel of figure below):
If the curator is curating as part of an Affiliation, this will be printed out "automatically." The curator who is saving the Classification as Provisional will be printed out upon submitting the form. The curator can add the date reviewed for Provisional Classification as well as additional comments pertaining to this review process. The timestamp of the submission will be saved and equivalent to the time at which the Provisional Classification is saved (Note: this could be different from the Date of Review).
Upon clicking "Preview Provisional" (a Preview step is required as Provisional Classifications cannot be edited -- new Provisional Classifications can be made), 3 options will appear:
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Cancel Provisional: resets all Provisional fields
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Edit Provisional: allows you to edit the information entered (date, additional comments)
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Submit Provisional: saves Provisional Classification -- once saved, no edits can be made, but the Evidence Summary for the Provisional Classification can always be viewed. If a second Provisional Classification is made, the first one will be archived, and its Evidence Summary will remain viewable (see below)
When a curator saves a new Provisional Classification, they will see an entry for it, with the ability to "View Provisional Summary" as well as an Approval box appear above. Clicking on the "View Provisional Summary" button will show you the Evidence Summary for your saved Provisional Classification. Note: This Provisional Classification cannot be edited, but it can always be viewed, even if a new Provisional Classification is saved.
On the banner underneath the header of each page in the GCI, you will also see the Provisional tag appear; if you are on the Record Curation Central page, you will also see "[View/Approve Current Provisional]" -- you can click on this to get back to the Approval form shown above.
NOTE: If changes are required following review of a Provisional Classification prior to approval, please follow the following steps:
- Add evidence
- View Classification Matrix
- Save new Summary Classification
- Create new Provisional -- this new one will become the current Provisional and the previous Provisional will become archived
When your Saved Provisional is ready to be Approved, you can Approve the Current Saved Provisional by clicking on the "[View/Approve Current Provisional]" link from the Record Curation Central page (or Approve it directly after saving the Provisional. Fill in the forms, much as was done when saving the Provisional:
Note that, if certain people have been designated to be an "Approver," their names will appear in the pull-down and this will be a required field.
Once you select "Preview Approval," you will be able to see the information (date, approver, additional comments) for the Approval and then, as for saving a Provisional, pick one of the 3 options:
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Cancel Approval: resets all Approval fields
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Edit Approval: allows you to edit the information entered (date, approver, additional comments)
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Submit Approval: saves Approved Classification -- once saved, no edits can be made, but the Evidence Summary for the Approved Classification can always be viewed. If a second Approved Classification is made, the first one will be archived, and its Evidence Summary will remain viewable (see below)
Once an Approved Classification is submitted, it will appear directly above the current saved Provisional (both will be marked with green flags). You will be able to see the Approved Classification at any time by clicking on the "View Approved Summary" button. Note: This Approved Classification cannot be edited, but it can always be viewed, even if a new Approved Classification is saved and it becomes archived.
Once a Classification has been Approved, this tag will appear in the header
Once either a Provisional or Approved Classification has been saved, a curator can still adjust evaluations or add new evidence and evaluate that evidence to create a New Saved Summary and then a new Provisional and Approved, if desired.
While new saved Summary Classifications will replace previous Summary Classifications, new Provisional and Approved Classifications will NOT replace/override their previous Provisional or Approved Classifications -- all previous Provisional and Approved Classifications will be archived, and their summaries viewable at any time via the "View Provisional Summary" and "View Approved Summary" buttons.
If new evaluations are made following Approval and a new Summary Classification is saved, the "New Saved Summary" button will also appear in the header
If this new saved Summary Classification (with or without modification) is saved as Provisional and an Approved Classification already exists, the new Provisional Classification will appear at the top with a green flag to mark it as the current Provisional Classification:
The New provisional button will appear in the header alongside the Approved button to indicate a new Provisional Classification has been made since the Approved one:
If on the Record Curation Central page, you will also see the ability to view the Evidence Summary for your current Approved Classification or to View or Approve the Current Provisional (New Provisional).
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Gene Curation Express, which was previously used by ClinGen curators to enter Classifications from spreadsheets onto the ClinGen website, was disabled when the "Publish" feature went live as part of release 20 (R20) of the GCI/VCI. From this point on all submissions of Approved Classifications to the ClinGen website need to be done only via the "Publish" feature in the GCI. If you wish to amend any of the Classifications that were added to the ClinGen website via Gene Curation Express, this will need to be requested via the ClinGen website help desk (clingen@clinicalgenome.org).
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Only Classifications with an 'Autosomal Dominant', 'Autosomal Recessive', or 'X-linked' mode of inheritance (i.e. those supported by the Clinical Validity Classification framework) should be published to the ClinGen website. Classifications with an "Unknown" or "Other" mode of inheritance will encounter an error. Additionally, as mitochondrial inheritance is not currently supported by the Classification framework, Classifications with mitochondrial inheritance should not be published to the website. The Gene Curation WG will work with the mitochondrial gene curation group to provide the ability to support this in the future.
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Currently, the disease for a Gene:Disease Classification must be annotated using a MONDO ID for that Classification to be successfully published to the website. Right now, Classifications with a free text term will encounter an error when one tries to publish them to the website. We are working to support the publication of free text disease terms on the website in the near future; however, MONDO IDs are still strongly encouraged whenever possible. If you are having trouble finding a MONDO term for your disease, please reach out to clingen-helpdesk@lists.stanford.edu and we will direct you appropriately.
Any user curating as part of a ClinGen Affiliation can publish to the ClinGen website (clinicalgenome.org). Publishing is currently restricted to ClinGen Affiliations only.
If you have migrated away from the Classification section then when you return you can open the "Publication Classification" panel by clicking the "Publish Summary" button associated with the current Approved Classification.
Alternatively, upon saving an Approved Classification a "Publish Classification" panel automatically opens up above the "Saved Approved and Provisional Classification(s)" table.
Most fields will be auto-filled but you do have the option of adding in any comments about the publishing process in the "Additional comments" box. To proceed with publishing click the "Preview Publish" button.
Once you select "Preview Publish," you will be able to see the information (affiliation, date published, publisher, additional comments) for the publication and then, as for saving a Provisional or Approved Classification, you can pick one of 3 options:
- Cancel Publish: resets all Publish fields
- Edit: allows you to edit the information entered (additional comments)
- Publish: publishes the Approved Classification to the ClinGen website -- once saved, no edits can be made.
Upon publishing, you will now see information about the Publish process in a panel under the Approved Classification to which it pertains. This panel contains information on who the Approved Classification was "Published by", its "Date published", any "Additional comments" that were saved, and a "Link" that is a direct linkout to the Approved Classification on the ClinGen website.
NOTE: although the newly published Approved Classification will appear almost immediately on the ClinGen website, it may take several minutes before it will appear in searches and/or lists.
The purple "PUBLISHED" icon is used to indicate that an Approved Classification has been published, it can be seen in the headers and on the dashboard.
If the Published Approved Classification is not the most recent Approved Classification, i.e. since it was published a new Classification has been Approved but not yet Published, then a purple warning triangle will be shown next to the purple "PUBLISHED" icon.
There are two ways to Unpublish an Approved Classification:
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If a second Approved Classification is published, the first one will be automatically unpublished. Details of the Unpublishing are shown below the now archived (previously Approved) Classification, such as who it was "Unpublished by", its "Date unpublished", and any "Additional comments" that were saved. It's unpublished status is also indicated by the "UNPUBLISHED" icon.
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A current Published Approved Classification can be Unpublished at any time simply by clicking on the "Unpublish Summary" button found under that Classification.
Upon clicking the "Unpublish Summary" button an "Unpublish Classification" panel opens up above the "Saved Approved and Provisional Classification(s)" table.
Most fields will be auto-filled but you do have the option of adding in any comments about the unpublishing process in the "Additional comments" box. To proceed with unpublishing click the "Preview Unpublish" button.
Once you select "Preview Unpublish," you will be able to see the information (affiliation, date unpublished, unpublished by, additional comments) for the unpublication and then, as for publishing an Approved Classification, you can pick one of 3 options:
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Cancel Unpublish: resets all Unpublish fields
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Edit: allows you to edit the information entered (additional comments)
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Unpublish: unpublishes the Approved Classification from the ClinGen website -- once saved, no edits can be made.
Details of the Unpublishing are shown below the now archived (previously Approved) Classification, such as who it was "Unpublished by", its "Date unpublished", and any "Additional comments" that were saved. Its unpublished status is also indicated by the "UNPUBLISHED" icon.
NOTE: it may take several minutes before the Classification disappears from all locations on the ClinGen website, so please allow up to 15 minutes before confirming that it has been unpublished.