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(RPGR):c.1100del (p.Pro367fs)

CA226343

98728 (ClinVar)

Gene: RPGR (HGNC:6103)

Condition: RPGR-related retinopathy (MONDO:0100437)

Inheritance Mode: X-linked inheritance (primarily recessive with milder female expression)

UUID: ae32c582-19d1-42ce-958d-43011fbc888e

Approved on: 2025-08-01

Published on: 2025-08-01

HGVS expressions

NM_001034853.2(RPGR):c.1100del (p.Pro367fs)

NM_001034853.2:c.1100del

NC_000023.11:g.38299102del

CM000685.2:g.38299102del

NC_000023.10:g.38158355del

CM000685.1:g.38158355del

NC_000023.9:g.38043299del

NG_009553.1:g.33435del

ENST00000494707.6:c.304del

ENST00000642170.1:n.1354del

ENST00000642395.2:c.1100del

ENST00000642558.1:c.1007del

ENST00000642739.1:c.1100del

ENST00000644238.1:c.1060-1649del

ENST00000644337.1:c.1060-1649del

ENST00000645032.1:c.1100del

ENST00000645124.1:c.1100del

ENST00000646020.1:c.1160del

ENST00000318842.11:c.1100del

ENST00000339363.7:c.1100del

ENST00000378505.6:c.1100del

ENST00000464437.1:c.166del

ENST00000465127.1:c.172-367019del

ENST00000474584.5:c.1100del

ENST00000482855.5:c.1100del

ENST00000494841.1:n.363del

NM_000328.2:c.1100del

NM_001034853.1:c.1100del

NM_001367245.1:c.1097del

NM_001367246.1:c.1060-1649del

NM_001367247.1:c.1100del

NM_001367248.1:c.1130del

NM_001367249.1:c.1097del

NM_001367250.1:c.1097del

NM_001367251.1:c.1060-1649del

NR_159803.1:n.1302del

NR_159804.1:n.1151del

NR_159805.1:n.1242del

NR_159806.1:n.1242del

NR_159807.1:n.1242del

NR_159808.1:n.1354del

NM_000328.3:c.1100del

Pathogenic

PM2_Supporting PVS1 PS4_Supporting

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.1100del (p.Pro367LeufsTer14) is a frameshift variant due to deletion of 1 nucleotide and introduces a premature stop codon after 14 amino acids in exon 10 of 15 that is predicted to result in nonsense-mediated decay (PVS1). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). This variant has been reported in at least 2 apparently unrelated probands meeting one of the PS4 requirements of a male with some functional vision impairment by age 30 years and/or decreased or absent electroretinogram responses, or a female with functional visual abnormality and documentation of a male relative affected with retinitis pigmentosa (PMID: 36017691, PMID: 10937588, PS4_Supporting). 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, PS4_Supporting and PM2_Supporting. (date of approval 05/16/2025).

PM2_Supporting

This variant is absent from gnomAD v4.0.0 (PM2_Supporting).

PVS1

This is a frameshift 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_Supporting

This variant has been reported in at least 2 apparently unrelated probands meeting one of the PS4 requirements of a male with some functional vision impairment by age 30 and/or decreased or absent ERG responses, or a female with functional visual abnormality and documentation of a male relative affected with retinitis pigmentosa (PMIDs: 36017691 and 10937588, PS4_Supporting).

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.