Submissions for variant NM_000322.5(PRPH2):c.634A>G (p.Ser212Gly)

dbSNP: rs61755800

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
NEI Ophthalmic Genomics Laboratory, National Institutes of Health	RCV000504657	SCV001424602	likely pathogenic	Retinitis pigmentosa	2020-01-07	criteria provided, single submitter	clinical testing	The variant NM_000322.4:c.634A>G in the PRPH2 gene has been previously studied(PMIDs 1427912, 18050133, 30924848). 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 (rs61755800,CM920606). It is absent in gnomAD browser. It is not enriched in the PRPH2 disease cohort. We invoked ACMG criteria [PP1-M, PM1, PM2, PM5, PP3, PP5] and classified NM_000322.4:c.634A>G in the PRPH2 gene as a Likely Pathogenic mutation.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000085000	SCV001446851	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001854491	SCV002243017	pathogenic	PRPH2-related disorder	2022-09-07	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 98689). This missense change has been observed in individuals with PRPH2-related conditions (PMID: 1427912, 18050133; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 212 of the PRPH2 protein (p.Ser212Gly).
Dept Of Ophthalmology, Nagoya University	RCV003888459	SCV004707340	likely pathogenic	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV003888459	SCV005070977	likely pathogenic	Retinal dystrophy	2020-01-01	criteria provided, single submitter	clinical testing
Retina International	RCV000085000	SCV000117136	not provided	not provided		no assertion provided	not provided
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000504657	SCV000598703	likely pathogenic	Retinitis pigmentosa	2015-01-01	no assertion criteria provided	research
Leiden Open Variation Database	RCV000085000	SCV001745094	likely pathogenic	not provided	2021-04-06	no assertion criteria provided	curation	Curator: Global Variome, with Curator vacancy. Submitters to LOVD: LOVD, Manon Peeters, Yoshito Koyanagi.