Submissions for variant NM_014249.4(NR2E3):c.166G>A (p.Gly56Arg)

gnomAD frequency: 0.00001  dbSNP: rs121912631

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000286602	SCV000227426	pathogenic	not provided	2015-05-18	criteria provided, single submitter	clinical testing
UCLA Clinical Genomics Center, UCLA	RCV000005871	SCV000255426	likely pathogenic	Retinitis pigmentosa 37	2013-02-05	criteria provided, single submitter	clinical testing
GeneDx	RCV000286602	SCV000330651	pathogenic	not provided	2022-08-04	criteria provided, single submitter	clinical testing	Published functional studies demonstrate a damaging effect (impact on DNA binding and dimerization of transcription factor NR2E3) (PMID: 19823680, 27013732); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 19006237, 26910043, 22661467, 17982421, 32037395, 19898638, 27013732, 32531858, 29034877, 33576794, 30718709, 25326637, 33807610, 31054281, 24938718, 17564971, 19823680)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000286602	SCV001205035	pathogenic	not provided	2023-11-13	criteria provided, single submitter	clinical testing	This sequence change replaces glycine with arginine at codon 56 of the NR2E3 protein (p.Gly56Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant retinitis pigmentosa (PMID: 17564971, 17982421, 19006237, 26910043). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 5533). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NR2E3 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects NR2E3 function (PMID: 19006237, 19823680). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics	RCV001075751	SCV001241381	pathogenic	Retinal dystrophy	2019-06-05	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000286602	SCV001447300	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000005871	SCV002526723	pathogenic	Retinitis pigmentosa 37	2022-05-30	criteria provided, single submitter	clinical testing	_x000D_ Criteria applied: PS1, PS4, PP1_STR, PS3_MOD, PM2_SUP
Dept Of Ophthalmology, Nagoya University	RCV001075751	SCV004707823	pathogenic	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
OMIM	RCV000005871	SCV000026053	pathogenic	Retinitis pigmentosa 37	2007-07-01	no assertion criteria provided	literature only
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000787628	SCV000926613	pathogenic	Retinitis pigmentosa	2018-04-01	no assertion criteria provided	research
Clinical Genetics Laboratory, University Hospital Schleswig-Holstein	RCV000005871	SCV002583439	pathogenic	Retinitis pigmentosa 37	2022-05-02	no assertion criteria provided	clinical testing