ClinVar Miner

Submissions for variant NM_014249.4(NR2E3):c.364C>T (p.Arg122Cys)

gnomAD frequency: 0.00002  dbSNP: rs527236086
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000670387 SCV000795232 uncertain significance Enhanced S-cone syndrome; Retinitis pigmentosa 37 2017-11-01 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001075734 SCV001241363 pathogenic Retinal dystrophy 2019-05-19 criteria provided, single submitter clinical testing
Invitae RCV001205439 SCV001376696 pathogenic not provided 2024-01-24 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 122 of the NR2E3 protein (p.Arg122Cys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with clinical features of autosomal recessive NR2E3-related conditions (PMID: 24339724, 30324420, 32037395; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 143147). 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%. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV001831925 SCV004191592 likely pathogenic Enhanced S-cone syndrome 2023-10-14 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003935226 SCV004752276 likely pathogenic NR2E3-related condition 2024-02-07 criteria provided, single submitter clinical testing The NR2E3 c.364C>T variant is predicted to result in the amino acid substitution p.Arg122Cys. This variant has been reported in the homozygous state in two siblings with retinitis pigmentosa from a consanguineous family (Family RP670, Bocquet et al. 2013. PubMed ID: 24339724). This variant has also been reported in the homozygous and compound heterozygous states in additional unrelated individuals with retinal dystrophies (Murro et al. 2018. PubMed ID: 30324420; Patient K6189, Table S6, Oishi et al. 2014. PubMed ID: 25324289; Table S2, Zampaglione et al. 2020. PubMed ID: 32037395). This variant is reported in 0.0081% of alleles in individuals of East Asian descent in gnomAD. Given the evidence, we interpret this variant as likely pathogenic.
Department of Ophthalmology and Visual Sciences Kyoto University RCV000132672 SCV000172623 probable-pathogenic Retinitis pigmentosa no assertion criteria provided not provided Converted during submission to Likely pathogenic.
Natera, Inc. RCV001831925 SCV002085603 uncertain significance Enhanced S-cone syndrome 2020-04-16 no assertion criteria provided clinical testing

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