Submissions for variant NM_006445.4(PRPF8):c.6928A>G (p.Arg2310Gly)

dbSNP: rs752997229

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001231748	SCV001404280	pathogenic	not provided	2023-07-17	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects PRPF8 function (PMID: 28515276). 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 PRPF8 protein function. ClinVar contains an entry for this variant (Variation ID: 438226). This missense change has been observed in individuals with autosomal dominant retinitis pigmentosa (PMID: 11468273, 12714658, 16799052). It has also been observed to segregate with disease in related individuals. This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 2310 of the PRPF8 protein (p.Arg2310Gly).
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV000504770	SCV001950340	pathogenic	Retinitis pigmentosa	2021-04-01	criteria provided, single submitter	curation	The p.Arg2310Gly variant in PRPF8 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: PM2, PP3, PS3, PM1, PP1. 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.
Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel	RCV000504770	SCV004030276	pathogenic	Retinitis pigmentosa	2023-07-24	criteria provided, single submitter	research	Clinical significance based on ACMG v2.0
Dept Of Ophthalmology, Nagoya University	RCV003889914	SCV004706136	likely pathogenic	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV003889914	SCV005072607	likely pathogenic	Retinal dystrophy	2020-01-01	criteria provided, single submitter	clinical testing
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV001542603	SCV005417696	pathogenic	Retinitis pigmentosa 13		criteria provided, single submitter	clinical testing	PM2_Supporting+PS3+PP2+PS4_Moderate+PP4+PP1
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000504770	SCV000599196	likely pathogenic	Retinitis pigmentosa	2015-01-01	no assertion criteria provided	research
Faculty of Health Sciences, Beirut Arab University	RCV001257799	SCV001434677	pathogenic	Autosomal dominant retinitis pigmentosa	2019-08-11	no assertion criteria provided	literature only
Genomics England Pilot Project, Genomics England	RCV001542603	SCV001760396	pathogenic	Retinitis pigmentosa 13		no assertion criteria provided	clinical testing