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ClinGen Dosage Sensitivity Curation Module - Version 2024
 Available for current members of ClinGen Gene Curation Expert Panels (GCEPs)

ClinGen Dosage Sensitivity Curation Module 2024 Version

Date of Release:

Expiration Date: December 31, 2024

Credits offered: CME, NSGC Category 2 (Self-report)

Estimate time of completion: 5 hours per curation (limit of up to 10 curations)

Course must be completed by the expiration date



Course Description:

The Clinical Genome Resource (ClinGen, is an NIH-funded resource dedicated to building an authoritative central resource that defines the clinical relevance of genes and variants for use in precision medicine and research (Strande et al. 2017). Dosage Sensitivity Curation evaluates genes and genomic regions for haploinsufficiency or triplosensitivity. Haploinsufficiency (HI) is when one copy of a gene or genomic region is lost and results in a consistent phenotype and triplosensitivity (TS) is when there is an extra copy of a gene or genomic region that results in a consistent phenotype. Each gene and genomic region evaluated receives a separate HI score and TS score.

From 2011-2019, the dosage sensitivity curation process was based on the framework published in Riggs et al. 2012. Beginning in February 2019, the group adopted a more stringent evaluation ( process for single gene evaluations consistent with the recommendations for evaluating probands identified in the literature, public databases, and/or internal databases (henceforth referred to as “probands”) as described in the American College of Medical Genetics and Genomics (ACMG) and ClinGen technical standards for the interpretation of constitutional CNVs.

There are currently three subgroups within ClinGen’s dosage sensitivity curation team:

  • Neurodevelopmental Dosage Subgroup: Evaluating genes implicated in neurodevelopmental disorders (NDDs), including intellectual disability (ID), developmental delays (DD), autism, seizures, etc.
  • Hereditary Cancer Subgroup: Evaluating genes implicated in hereditary cancer
  • Genomic Regions (Recurrent CNV) Subgroup: Developing additional considerations for the evaluation of recurrent CNVs, including regions associated with low penetrance

The Neurodevelopmental Dosage Subgroup and the Hereditary Cancer Subgroup typically focus on single gene evaluations, while the Recurrent CNV subroup focuses on evaluation of genomic regions with recurrent breakpoints mediated by genomic architecture, such as segmental duplications. In most cases, curators in the group complete the initial dosage sensitivity curation and arrive at a provisional score, followed by presentation of the data to the subgroup for review and final approval.

The Dosage Sensitivity Curation Task Teams utilize the ClinGen Dosage Curation Interface (DCI) for documentation of dosage sensitivity haploinsufficiency and triplosensitivity classifications, and all curations completed by the group are made publicly available through the ClinGen website (

Target Audience:

This ClinGen Dosage Sensitivity curation module is intended to provide learners with educational credit for participating in ClinGen dosage curation activities and is available to individuals who are existing members of the ClinGen Dosage Sensitivity Working Group and have had at least one dosage curation previously approved by a ClinGen Dosage Sensitivity subgroup.

Learning Objectives:


At the conclusion of this session, participants should be able to:

  • Use the ClinGen vetted dosage sensitivity curation process to evaluate the strength of evidence supporting or refuting a claim that variants result in loss of function in a gene of interest
  • Perform a literature search to identify relevant publications to support a dosage curation
  • Score collected/collated evidence in the DCI to determine a provisional score for haploinsufficiency and triplosensitivity based on guidelines
  • Present evidence summary supporting provisional score to dosage sensitivity subgroup
  • Publish approved dosage curation to

Course References:

Riggs, E. R., Church, D. M., Hanson, K., Horner, V. L., Kaminsky, E. B., Kuhn, R. M., . . . Martin, C. L. (2012). Towards an evidence-based process for the clinical interpretation of copy number variation. Clinical Genetics, 81(5), 403-412. doi:10.1111/j.1399-0004.2011.01818.x [doi]


Planning and Faculty

Erica Andersen, PhD, FACMG

Section Chief: Cytogenetic and Genomic Microarray, Assistant Professor, University of Utah School of Medicine

ARUP Laboratories

Salt Lake City, UT 84108


Erin Rooney Riggs, MS, CGC

Assistant Professor

Autism & Developmental Medicine Institute


Lewisburg, PA 17837



Accredited Continuing Education Information

Continuing Medical Education (CME AMA & CME Other)


This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of The American College of Medical Genetics and ClinGen - Clinical Genome Resource Genomics and is accredited by the ACCME to provide continuing medical education for physicians.


Credit Designation
The American College of Medical Genetics and Genomics designates this enduring material activity for a maximum of 5 hours in AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.


National Society of Genetic Counselors (NSGC)

This activity meets requirements to apply for Category 2 CEUs from the National Society of Genetic Counselors (NSGC). Please complete the module and submit your certificate to NSGC, using the instructions here. ACMG is the accredited sponsor. You must apply within three months of the activity date, but you will be able to submit up to 10 curations under one fee for this activity.


Learner Data Consent

ACMG Education reports learner data to respective agency boards and you will be asked for consent during the evaluation process. Your compliance with deadlines and completing evaluations are part of the process in meeting learner needs and ACMG’s education mission.


Claiming your Educational Credits

  • Invitation code
  • Provide a record of a ClinGen Dosage Sensitivity Working Group-approved, published classification below, including:
    • Gene or Region Name/Description
    • Disease Name if applicable
    • URL of Dosage Sensitivity Curation
    • Upload a PDF of the final evidence summary from the DCI
    • Haploinsufficiency and Triplosensitivity Score Approval Date
  • Evaluation and self-report in the ACMG Genetics Academy Click here (required for educational credits)

Estimated time of Completion: Up to 5 hours per curation

Please note: In the Self Report section, you will be asked how many CMEs are requested. 1 CME is the

equivalent of one hour. Please use that field to document the number of hours (maximum of 5) you spent gathering, evaluating and scoring evidence as well as presenting to the Dosage Sensitivity Working Group for approval.

Financial Disclosures

Accredited Continuing Education Financial Disclosure

The American College of Medical Genetics and Genomics (ACMG) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide Accredited Continuing Education (ACE) for physicians. ACMG is an organization committed to improvement of patient care and general health by the incorporation of genetics and genomics into clinical practice.


ACMG has implemented the following procedures to ensure the independence of ACE activities from commercial influence/promotional bias, the Accreditation Council for Continuing Medical Education (ACCME) requires that providers (ACMG) must be able to demonstrate that: 1) everyone in a position to control the content of an ACE activity has disclosed all financial relationships that they have had in the past 24 months with ineligible* companies; 2) ACMG has implemented a mechanism to mitigate relevant financial relationships; and 3) all relevant financial relationships with ineligible companies are disclosed to the learners before the beginning of the educational activity. The learners must also be informed if no relevant financial relationships exist.
*Ineligible companies are defined as those whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.


ACMG Education Policies

Please review the policies below regarding the ACMG Education program


All of the relevant financial relationships listed for these individuals have been mitigated.



Program Committee Member | Reviewer

Financial Disclosure Relationship/Company

Erica Andersen, PhD, FACMG

Consultant: AbbVie, Bionano Genomics

Erin Rooney Riggs, MS, CGC

Consultant : Illumina, Inc.



ACMG educational programs are designed primarily as an educational tool for health care providers who wish to increase their understanding of the application of genomic technologies to patient care. The ACMG does not endorse or recommend the use of this educational program to make patient diagnoses, particular by individuals not trained in medical genetics. Adherence to the information provided in these programs does not necessarily ensure a successful diagnostic outcome. The program should not be considered inclusive of all proper procedures and or exclusive of other procedures and that are reasonably directed at obtaining the same results. In determining the propriety of any specific procedure or, a healthcare provider should apply his or her own professional judgment to the specific clinical circumstances presented by the individual patient or specimen.

Questions regarding CE credit should be directed to


Availability: On-Demand
Expires on Dec 31, 2024
Cost: FREE
Credit Offered:
5 CME (AMA) Credits
5 CME (Other) Credits

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