# Integrative Curation of Clinically Relevant Variants in X-Linked Inherited Retinal Disease Genes

> **NIH NIH U24** · BAYLOR COLLEGE OF MEDICINE · 2022 · $351,997

## Abstract

Abstract
Inherited retinal diseases (IRD) are a major cause of early-onset blindness, profoundly affecting millions of
patients. Given the clinical and genetic heterogeneity of IRD, targeted gene therapy is emerging as the main
effective approach for treating the disease with many clinical trials currently underway. To maximize the benefit
of these emerging therapies to patients, molecular diagnosis is the first critical step.
In coordinating with the ClinGen Ocular Clinical Domain Working Group committee, we propose to establish a
new variant curation expert panel (VCEP) that will focus on developing disease and gene specifications and
curating expert assessment of variants in the seven X-linked IRD genes, including RPGR, CHM, RS1, RP2,
OFD1, NDP, and CACNA1F. Collectively, mutations in these genes account for 15% of IRD patients. We have
identified a distinguished panel of scientists across the world who will commit to this effort with diverse expertise:
practicing ophthalmologic physicians, clinical diagnostic laboratory directors, and world-leading researchers
studying the function of the X-linked IRD genes in the clinical and research domains. These experts bring
complementary knowledge and resources to this effort including functional laboratory assays to assess the
impact of patient variants, clinical trials for gene-based treatments, and collections of patient samples with
sequenced variants and a detailed clinical history.
Together with dedicated bioinformatics, curatorial, and administrative support, the X-linked IRD Variant Curation
Panel proposed will deploy the FDA approved ClinGen infrastructure tools and processes in combination with
the supportive resources we propose to collect, organize and provide to the panel to develop rule specifications
for X-linked IRD gene curation. With our panel and team of coordinated curation volunteers, we will curate and
expertly assess the variants in these genes. The products of this effort will be two-fold. First, specifications that
can be applied to assess new variants in the seven genes and can be adapted for other X-linked IRD genes.
And second, curated variants in the seven X-linked IRD genes with three-star (expert panel assessed) ratings in
the ClinVar databasethat will improve the assessment of de novo patient variants and enable treatments with
gene-based therapies.

## Key facts

- **NIH application ID:** 10413460
- **Project number:** 1U24EY032451-01A1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** KIM C WORLEY
- **Activity code:** U24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $351,997
- **Award type:** 1
- **Project period:** 2022-08-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10413460

## Citation

> US National Institutes of Health, RePORTER application 10413460, Integrative Curation of Clinically Relevant Variants in X-Linked Inherited Retinal Disease Genes (1U24EY032451-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10413460. Licensed CC0.

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