Variant Submission

Preparing to Submit a CPAM Nomination

To streamline the nomination process and ensure completeness, nominators are encouraged to gather key information before beginning the CPAM intake form. The form dynamically adjusts based on the nominator’s role (e.g., clinician, researcher, patient advocate) and the classification of the variant being submitted (e.g., Variant of Uncertain Significance [VUS] vs. Likely Pathogenic/Pathogenic).

Regardless of variant classification or nominator type, everyone will need to enter the following information:

  • Contact information (name, affiliation, email, phone)
  • HGVS variant description (e.g., NM_000000.0(GENE): c.123A>C (p.Glu41Asp))
  • Variant classification (Benign, Likely Benign, VUS, Likely Pathogenic, Pathogenic)
  • Sequencing data availability (optional: Yes/No)
  • Patient status (Has the variant been reported in a patient? Published? Contactable?)

Click a checklist to expand and see details:

Checklist for Variants of Uncertain Significance (VUS)
  • Gene–disease association status
  • Pathogenicity evidence (that you are aware of, e.g., phenotypic match, case reports, databases, in silico prediction, segregation, de novo, prior functional studies, etc.)
  • Additional questions based on role (see below):
  • for Patient/Advocate nominations:
    • Indicate researchers/labs for follow-up (if yes, provide contact information)
  • for Clinician nominations:
    • De-identified patient/clinical information (if in contact with patient)
      • Diagnosis
      • Phenotypic features
      • General demographic information
      • Family history
      • Variant inheritance and ACMG summary
      • Sequencing or clinical test details
      • Other variants
    • Indicate researchers/labs for follow-up (if yes, provide contact information)
  • for Researcher nominations:
    • If in contact with the patient – see the patient/clinical information list above.
    • Lab capabilities (website, relevant publication, or brief description)
    • Anticipated challenges/timeline
    • Collaborations/human-based studies
Checklist for Non-VUS Variants
  • Model preference & ranking (e.g., cell lines, zebrafish, mouse, and rat – can select multiple)
  • Model database search + justification (i.e., does a similar model already exist?)
  • Goal of model (brief description)
  • Additional questions based on role (see below):
  • for Patient/Advocate nominations:
    • Indicate researchers/labs for follow-up (if yes, provide contact information)
  • for Clinician nominations:
    • Expected phenotypic readouts
    • De-identified patient/clinical information (if in contact with patient)
      • Diagnosis
      • Phenotypic features
      • General demographic information
      • Family history
      • Variant inheritance and ACMG summary
      • Sequencing or clinical test details
      • Other variants
    • Indicate researchers/labs for follow-up (if yes, provide contact information)
  • for Researcher nominations:
    • If in contact with the patient – see the patient/clinical information list above.
    • Expected phenotypic readouts
    • Lab capabilities (website, relevant publication, or brief description)
    • Anticipated challenges/timeline
    • Collaborations/human-based studies

Ready to Submit?

Go to variant submission form

What happens following variant submission:

1. The application is submitted

The Pre-Clinical Section of CPAM is notified and the nominator is contacted to confirm we have received the application.

2. Consenting

If the application requires the collection of protected health information (PHI), we will share our contact information with the nominator and schedule a consenting appointment with the individual or legal guardians of the individual whose health records we will collect as part of our intake process. This information will be secured on a HIPAA-compliant server.

3. Case Evaluation

The Pre-Clinical and Bioinformatics sections of CPAM evaluate the case and prepare a presentation. The Pre-Clinical team will generate a deidentified summary of the clinical data and will pass this to the bioinformatics team to provide further information about the potential molecular impact of the variant.

4. CPAM Application Review Committee

Once the work-up is completed, the case is ready for final review by the CPAM Application Review Committee, who will determine whether the case is a fit for CPAM and what models will be generated.