# Development of recommendations and policies for genetic variant reclassification

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $682,898

## Abstract

Project Abstract
As genomic sequence data are being produced faster and at lower cost, the most significant
challenge in clinical genetic testing today is variant classification. Currently, there are marked
differences in variant classification among clinical laboratories, with clinically significant
discrepancies in 29% of variants interpreted. Variants that were previously categorized as
pathogenic are now known to be benign with the increasing availability of more ethnically diverse
reference data, and this is issue is more common for individuals of non-European ancestry. At
the same time, a substantial percentage of variants are classified as of unknown significance
(VUS), with inadequate data to prove or disprove a pathogenic association with a medical
condition. Progress in interpreting genomic data, however, will lead to greater agreement on how
to call variants that are currently subject to discrepant classifications and the question arises about
how will that information about reclassification of variants reach patients and their health care
providers. There is currently no definitive guidance from professional organizations or opinion
leaders about how to handle variant reclassification, and the field seems uncertain how to
respond. Stakeholders including laboratories, providers, patients, and payers likely have different
perspectives and opinions. To provide an empirical foundation for this critical discussion and
develop guidance for the field, we will conduct a series of activities including focus groups and
online surveys with 3 key stakeholder groups: patients, providers, and the laboratories. We will
have three working groups to define the legal, ethical, and economic aspects to consider and
develop possible solutions. We will host an annual meeting with experts on genetics, clinical
laboratory operations, reimbursement, health economists, regulatory and legal issues, and ethics,
along with clinicians and patient advocates, to provide guidance for the project, to review the data
and develop a set of options and a final set of recommendations to address this issue. We will
seek input on possible solutions from stakeholders through an online survey and arrive at final
recommendations that we will present to the genomics community and to board of the American
College of Medical Genetics and Genomics to guide the adoption of an acceptable and
responsible policy in for this rapidly changing area.

## Key facts

- **NIH application ID:** 10218237
- **Project number:** 5R01HG010365-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Paul Stuart Appelbaum
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $682,898
- **Award type:** 5
- **Project period:** 2018-09-24 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10218237

## Citation

> US National Institutes of Health, RePORTER application 10218237, Development of recommendations and policies for genetic variant reclassification (5R01HG010365-04). Retrieved via AI Analytics 2026-06-10 from https://api.ai-analytics.org/grant/nih/10218237. Licensed CC0.

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