Submissions for variant NM_000322.5(PRPH2):c.664T>C (p.Cys222Arg)

dbSNP: rs1554269053

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002524400	SCV003439334	pathogenic	PRPH2-related disorder	2022-03-28	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Cys222 amino acid residue in PRPH2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 28559085; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: 437967). This missense change has been observed in individuals with autosomal dominant PRPH2-related conditions (PMID: 28041643, 31456290). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 222 of the PRPH2 protein (p.Cys222Arg).
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV000504883	SCV005071073	pathogenic	Retinal dystrophy	2020-01-01	criteria provided, single submitter	clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000504883	SCV000598704	likely pathogenic	Retinal dystrophy	2015-01-01	no assertion criteria provided	research
Sharon lab, Hadassah-Hebrew University Medical Center	RCV001003140	SCV001161209	likely pathogenic	Retinitis pigmentosa	2019-06-23	no assertion criteria provided	research