ClinVar Miner

Submissions for variant NM_000322.5(PRPH2):c.499G>A (p.Gly167Ser)

dbSNP: rs527236098
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000438661 SCV000524231 likely pathogenic not provided 2018-07-15 criteria provided, single submitter clinical testing The G167S variant in the PRPH2 gene has been reported previously in association with PRPH2-related retinal dystrophies (Testa et al., 2005; Jin et al., 2008; Zaneveld et al., 2015). The G167S variant is not observed in large population cohorts (Lek et al., 2016). The G167S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Missense variants in the same codon (G167D) and in nearby residues (C165R/Y, D170S, R172W/G/Q) have been reported in the Human Gene Mutation Database in association with PRPH2-related retinal dystrophies (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret G167S as a likely pathogenic variant.
Invitae RCV001055454 SCV001219847 pathogenic PRPH2-related disorder 2024-01-20 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 167 of the PRPH2 protein (p.Gly167Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant pattern dystrophy or retinitis pigmentosa (PMID: 16024869, 23591405, 25324289, 28559085). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 143070). 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 PRPH2 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001073378 SCV001238919 pathogenic Retinal dystrophy 2019-01-04 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000438661 SCV001246206 pathogenic not provided 2019-02-01 criteria provided, single submitter clinical testing
NEI Ophthalmic Genomics Laboratory, National Institutes of Health RCV001250331 SCV001424651 likely pathogenic Stargardt disease 2020-01-07 criteria provided, single submitter clinical testing The variant NM_000322.4:c.499G>A in the PRPH2 gene has been previously studied(PMIDs 16024869, 22863181, 23591405, 25324289, 25474345, 28559085). We found this variant in 1 patient(s) in a PRPH2 cohort study (Reeves et al. 2020). This variant is listed in dbSNP and/or HGMD (rs527236098,CM052911). It is absent in gnomAD browser. It is not enriched in the PRPH2 disease cohort. We invoked ACMG criteria [PM1, PM2, PM5, PP1, PP3, PP5] and classified NM_000322.4:c.499G>A in the PRPH2 gene as a Likely Pathogenic mutation.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000438661 SCV001448002 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV000438661 SCV004026291 pathogenic not provided 2023-02-28 criteria provided, single submitter clinical testing PM1, PP3, PM5, PP4, PS4, PM2_SUP
Dept Of Ophthalmology, Nagoya University RCV001073378 SCV004707353 likely pathogenic Retinal dystrophy 2023-10-01 criteria provided, single submitter research
Department of Ophthalmology and Visual Sciences Kyoto University RCV000132579 SCV000172522 pathogenic Retinitis pigmentosa no assertion criteria provided not provided Converted during submission to Pathogenic.
Leiden Open Variation Database RCV000438661 SCV001744954 pathogenic not provided 2021-06-19 no assertion criteria provided curation Curator: Global Variome, with Curator vacancy. Submitters to LOVD: LOVD, Manon Peeters, Yoshito Koyanagi.

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