ClinVar Miner

Submissions for variant NM_000322.5(PRPH2):c.659G>A (p.Arg220Gln)

gnomAD frequency: 0.00001  dbSNP: rs61755810
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV001075618 SCV001241245 likely pathogenic Retinal dystrophy 2019-02-06 criteria provided, single submitter clinical testing
Invitae RCV001346727 SCV001540952 pathogenic PRPH2-Related Disorders 2022-12-14 criteria provided, single submitter clinical testing This variant disrupts the p.Arg220 amino acid residue in PRPH2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9443872, 16916875, 17653047; 29555955.). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects PRPH2 function (PMID: 26796962). 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: 98699). This missense change has been observed in individuals with PRPH2-related conditions (PMID: 8994365, 30822235). This variant is present in population databases (rs61755810, gnomAD 0.004%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 220 of the PRPH2 protein (p.Arg220Gln).
GeneDx RCV000085011 SCV001765310 likely pathogenic not provided 2023-04-12 criteria provided, single submitter clinical testing Identified in patients with vitelliform macular dystrophy and pattern dystrophy in published literature (Keen and Inglehearn, 1996; George Priya Doss et al., 2014); Observed in homozygous state in a patient in published literature (Kahn et al., 2019) with pediatric-onset cone-rod dystrophy and not observed in homozygous state in controls. Heterozygous parents had macular abnormalities.; In vitro functional studies demonstrate enhanced splicing and increased protein expression in murine retinas, which may affect cone degeneration (Becirovic et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34411390, 34240658, 24629188, 8956033, 8675410, 30822235, 31456290, 26796962, 8994365, 36393903, 36648066)
Retina International RCV000085011 SCV000117147 not provided not provided no assertion provided not provided
Sharon lab, Hadassah-Hebrew University Medical Center RCV001003141 SCV001161210 likely pathogenic Retinitis pigmentosa 2019-06-23 no assertion criteria provided research
Leiden Open Variation Database RCV000085011 SCV001744990 pathogenic not provided 2021-04-06 no assertion criteria provided curation Curator: Global Variome, with Curator vacancy. Submitters to LOVD: Global Variome, with Curator vacancy, LOVD, Manon Peeters.

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