# Genomic Clinical Variant Expert Curation Panel for Monogenic Diabetes: A Gateway to Precision Medicine in Diabetes Mellitus

> **NIH NIH U24** · UNIVERSITY OF MARYLAND BALTIMORE · 2024 · $343,083

## Abstract

PROJECT SUMMARY
Diabetes mellitus, a heterogeneous group of diseases characterized by hyperglycemia, affects over 37 million
individuals in the United States and 422 million worldwide and is a leading cause of cardiovascular disease,
blindness, end-stage renal disease and death. Maternal diabetes is also associated with risk for poor
pregnancy outcomes. Highly penetrant genetic forms of diabetes including maturity onset diabetes of the
young (MODY), neonatal diabetes, and syndromes that comprise both diabetes and developmental and
intellectual disabilities account for at least 1% of diabetes, or over 340,000 cases nationwide. Distinguishing
these genetic forms of diabetes from type 1 (T1D) and type 2 diabetes (T2D) demonstrably improves glucose
control and quality of life by enabling replacement of invasive insulin treatment and/or ineffective oral treatment
with less invasive and more efficacious etiology-based oral or dietary treatment for the patients and their
affected family members. In some cases, the individualized treatment can ameliorate neurological dysfunction.
However, recent studies show that most cases are misdiagnosed. There are several barriers to improving the
diagnosis rate, including lack of awareness, clinical overlap with other diabetes types, expense of testing,
genetic heterogeneity and predominance of rare variants. With the advent of next generation sequencing
techniques, testing is becoming increasingly feasible and cost-effective, but for its true potential to be realized,
a systematic process for the pooling, annotation and curation of variants is needed. Thus, we have
established an international ClinGen Monogenic Diabetes Expert Panel (MDEP) with both Variant Curation
(VCEP) and Gene Curation (GCEP) components consisting over 60 members and have developed gene-
specific rules for classifying MODY variants, curated hundreds of variants for deposit into ClinVar, and curated
the relationship with diabetes of all genes asserted as MODY genes. We now propose to move another step
toward our goal of true precision medicine for diabetes mellitus through comprehensive curation of the
relationship of diabetes and congenital hyperinsulinemic hypoglycemia with 70+ genes which have been
proposed as monogenic diabetes genes and to develop and apply gene specific rules to the curation of
variants in monogenic forms of autoimmune diabetes and insulin resistance/lipodystrophies, which have
individualized treatment implications distinct from the MODYs, including the opportunity to prevent extra-
pancreatic disease in multi-organ autoimmune forms and to treat the underlying leptin deficiency found in many
lipodystrophies.

## Key facts

- **NIH application ID:** 10844391
- **Project number:** 5U24HD112205-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** TONI I. POLLIN
- **Activity code:** U24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $343,083
- **Award type:** 5
- **Project period:** 2023-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10844391

## Citation

> US National Institutes of Health, RePORTER application 10844391, Genomic Clinical Variant Expert Curation Panel for Monogenic Diabetes: A Gateway to Precision Medicine in Diabetes Mellitus (5U24HD112205-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10844391. Licensed CC0.

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