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.1120G>T (p.Glu374Ter)

CA226344

98729 (ClinVar)

Gene: RPGR (HGNC:6103)

Condition: RPGR-related retinopathy (MONDO:0100437)

Inheritance Mode: X-linked inheritance

UUID: 511d48a7-a3db-49a5-a51b-76e2da624d4b

Approved on: 2025-08-01

Published on: 2025-08-01

HGVS expressions

NM_001034853.2:c.1120G>T

NM_001034853.2(RPGR):c.1120G>T (p.Glu374Ter)

NC_000023.11:g.38299081C>A

CM000685.2:g.38299081C>A

NC_000023.10:g.38158334C>A

CM000685.1:g.38158334C>A

NC_000023.9:g.38043278C>A

NG_009553.1:g.33455G>T

ENST00000494707.6:c.324G>T

ENST00000642170.1:n.1374G>T

ENST00000642395.2:c.1120G>T

ENST00000642558.1:c.1027G>T

ENST00000642739.1:c.1120G>T

ENST00000644238.1:c.1060-1629G>T

ENST00000644337.1:c.1060-1629G>T

ENST00000645032.1:c.1120G>T

ENST00000645124.1:c.1120G>T

ENST00000646020.1:c.1180G>T

ENST00000318842.11:c.1120G>T

ENST00000339363.7:c.1120G>T

ENST00000378505.6:c.1120G>T

ENST00000464437.1:c.186G>T

ENST00000465127.1:c.172-367040C>A

ENST00000474584.5:c.1120G>T

ENST00000482855.5:c.1120G>T

ENST00000494841.1:n.383G>T

NM_000328.2:c.1120G>T

NM_001034853.1:c.1120G>T

NM_001367245.1:c.1117G>T

NM_001367246.1:c.1060-1629G>T

NM_001367247.1:c.1120G>T

NM_001367248.1:c.1150G>T

NM_001367249.1:c.1117G>T

NM_001367250.1:c.1117G>T

NM_001367251.1:c.1060-1629G>T

NR_159803.1:n.1322G>T

NR_159804.1:n.1171G>T

NR_159805.1:n.1262G>T

NR_159806.1:n.1262G>T

NR_159807.1:n.1262G>T

NR_159808.1:n.1374G>T

NM_000328.3:c.1120G>T

Pathogenic

PP4 PVS1 PM2_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.1120G>T (p.Glu374Ter) is a nonsense variant that substitutes a premature stop codon for amino acid 374 in exon 10 of 15 and is predicted to trigger nonsense-mediated decay (PVS1). This variant is absent from hemizygous individuals in gnomAD v4.1.0 (PM2_Supporting). At least one proband harboring this variant exhibits a phenotype including early onset (1 pt), electroretinogram responses consistent with retinitis pigmentosa (1 pt), night blindness (0.5 pts), visual field constriction (0.5 pts), and genotyping by next-generation sequencing panel that did not identify an alternative basis for retinal disease (2 pts), which together are specific for RPGR-related retinopathy (5 points, PMID: 32037395, PP4). 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 PP4. (date of approval 05/16/2025).

PP4

At least one proband harboring this variant exhibits a phenotype including early onset (1 pt), electroretinogram responses consistent with retinitis pigmentosa (1 pt), night blindness (0.5 pts), visual field constriction (0.5 pts), and genotyping by next-generation sequencing with a panel of genes that did not identify an alternative basis for retinal disease (2 pts), which together are specific for RPGR-related retinopathy (5 points, PMID: 32037395, PP4).

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).

PM2_Supporting

This variant is absent from hemizygous individuals in gnomAD v4.1.0 (PM2_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.