Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_001034853.2:c.1154T>A

CA412739890

Gene: RPGR (HGNC:6103)

Condition: RPGR-related retinopathy (MONDO:0100437)

Inheritance Mode: X-linked inheritance

UUID: 684c1552-de73-4aa0-8107-678b0d3c8597

Approved on: 2025-08-01

Published on: 2025-08-01

HGVS expressions

NM_001034853.2:c.1154T>A

NC_000023.11:g.38299047A>T

CM000685.2:g.38299047A>T

NC_000023.10:g.38158300A>T

CM000685.1:g.38158300A>T

NC_000023.9:g.38043244A>T

NG_009553.1:g.33489T>A

ENST00000494707.6:c.358T>A

ENST00000642170.1:n.1408T>A

ENST00000642395.2:c.1154T>A

ENST00000642558.1:c.1061T>A

ENST00000642739.1:c.1154T>A

ENST00000644238.1:c.1060-1595T>A

ENST00000644337.1:c.1060-1595T>A

ENST00000645032.1:c.1154T>A

ENST00000645124.1:c.1154T>A

ENST00000646020.1:c.1214T>A

ENST00000318842.11:c.1154T>A

ENST00000339363.7:c.1154T>A

ENST00000378505.6:c.1154T>A

ENST00000464437.1:c.220T>A

ENST00000465127.1:c.172-367074A>T

ENST00000474584.5:c.1154T>A

ENST00000482855.5:c.1154T>A

ENST00000494841.1:n.417T>A

NM_000328.2:c.1154T>A

NM_001034853.1:c.1154T>A

NM_001367245.1:c.1151T>A

NM_001367246.1:c.1060-1595T>A

NM_001367247.1:c.1154T>A

NM_001367248.1:c.1184T>A

NM_001367249.1:c.1151T>A

NM_001367250.1:c.1151T>A

NM_001367251.1:c.1060-1595T>A

NR_159803.1:n.1356T>A

NR_159804.1:n.1205T>A

NR_159805.1:n.1296T>A

NR_159806.1:n.1296T>A

NR_159807.1:n.1296T>A

NR_159808.1:n.1408T>A

NM_000328.3:c.1154T>A

Pathogenic

PM2_Supporting PP1 PVS1

PS4 PS3

Evidence Links 0

Expert Panel

X-linked Inherited Retinal Disease VCEP

Criteria Specification Information

Criteria Specification: ClinGen X-linked Inherited Retinal Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RPGR Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

X-linked Inherited Retinal Disease VCEP

NM_001034853.2(RPGR):c.1154T>A (p.Leu385Ter) is a nonsense variant that substitutes a premature stop codon for amino acid 385 in exon 10 of 15 and is predicted to trigger nonsense-mediated decay (PVS1). Fibroblast cells expressing the variant exhibit loss of RPGR localization to the ciliary axoneme (PMID: 33182541). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). The variant has been reported to segregate with retinal dystrophy through at least 2 affected meioses from 1 family (PP1; PMID: 37541846). In summary, this variant is classified as pathogenic for RPGR-related retinopathy based on the ClinGen X-linked Inherited Retinal Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RPGR Version 1.0.0; PVS1, PM2_Supporting, and PP1. (date of approval 05/16/2025).

PM2_Supporting

This variant is absent from gnomAD v4.1.0 (PM2_Supporting).

PP1

The variant has been reported to segregate with retinal dystrophy through at least 2 affected meioses from 1 family. (PP1; PMID: 37541846)

PVS1

This is a nonsense variant that introduces a premature stop codon between amino acids 1-1132 that is predicted to either trigger nonsense-mediated decay or to disrupt a critical C-terminal region required for proper glutamylation of RPGR (PVS1, PMID: 36445968).

PS4

This variant has been reported in at least 1 proband meeting the PS4 requirement of some functional vision impairment in affected males by age 30, with decreased or absent cone and/or rod ERG responses or a female with functional visual abnormality and documentation of a male relative affected with retinitis pigmentosa (PMID: 37541846). However, PS4_Supporting requires at least 2 unrelated probands, so this criterion was not met.

PS3

Fibroblast cells expressing the variant exhibit loss of RPGR localization to the ciliary axoneme (PMID: 33182541, PS3_Supporting). This code is not met as PVS1 has already been used to reward the predicted null impact.

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.