Submissions for variant NM_001034853.2(RPGR):c.3092del (p.Glu1031fs)

dbSNP: rs1186795749

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Blueprint Genetics	RCV001074314	SCV001239887	pathogenic	Retinal dystrophy	2019-06-29	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001090908	SCV001246679	pathogenic	not provided	2024-04-01	criteria provided, single submitter	clinical testing	RPGR: PVS1:Strong, PM1, PM2, PS4:Moderate
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV001251566	SCV001573326	pathogenic	Retinitis pigmentosa 3	2021-04-08	criteria provided, single submitter	research	The RPGR c.3092del variant was identified in an individual with retinitis pigmentosa with a presumed X-linked inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1, PP3, PM2, PP1-M. Based on this evidence we have classified this variant as Pathogenic.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001724237	SCV001950366	pathogenic	Retinitis pigmentosa	2021-04-01	criteria provided, single submitter	curation	The p.Glu1031GlyfsTer58 variant in RPGR was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PVS1, PP3, PM2, PP1-M. Based on this evidence we have classified this variant as Pathogenic. If you have any questions about the classification please reach out to the Pierce Lab.
3billion	RCV001251566	SCV002058896	pathogenic	Retinitis pigmentosa 3	2022-01-03	criteria provided, single submitter	clinical testing	Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). The variant has been reported at least twice as pathogenic/likely pathogenic (ClinVar ID: VCV000866381, PMID: 31645972). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
MGZ Medical Genetics Center	RCV002290587	SCV002580631	pathogenic	X-linked cone-rod dystrophy 1	2022-02-15	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV001090908	SCV002759696	pathogenic	not provided	2019-11-13	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002557909	SCV003445110	pathogenic	Primary ciliary dyskinesia	2023-10-05	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu1031Glyfs*58) in the RPGR (ORF15) gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 122 amino acid(s) of the RPGR (ORF15) protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with retinitis pigmentosa (PMID: 12657579, 18332319, 31804667). This variant is also known as ORF15+1339delA. ClinVar contains an entry for this variant (Variation ID: 866381). This variant disrupts a region of the RPGR (ORF15) protein in which other variant(s) (p.Leu1130Lysfs*13) have been determined to be pathogenic (PMID: 22264887; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV001090908	SCV003840811	pathogenic	not provided	2022-09-11	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation, as the last 122 amino acids are replaced with 57 different amino acids, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); Also known as ORF15+1339delA; This variant is associated with the following publications: (PMID: 33355362, 30567410, 24077912, 31804667, 31645972, 32795431, 12657579, 18332319, 18552978, 27798110)
Blueprint Genetics	RCV001251566	SCV001427346	pathogenic	Retinitis pigmentosa 3		no assertion criteria provided	clinical testing