Submissions for variant NM_000539.3(RHO):c.83A>G (p.Gln28Arg)

dbSNP: rs1553780837

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001296378	SCV001485341	pathogenic	not provided	2024-04-09	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 28 of the RHO protein (p.Gln28Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of autosomal dominant retinitis pigmentosa (PMID: 28041643, 32581362; Invitae). ClinVar contains an entry for this variant (Variation ID: 437998). 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 RHO protein function with a positive predictive value of 95%. This variant disrupts the p.Gln28 amino acid residue in RHO. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8406457, 24106275, 29847639, 30977563). 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.
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004817727	SCV005071693	pathogenic	Retinal dystrophy	2023-01-01	criteria provided, single submitter	clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000505117	SCV000598754	likely pathogenic	Retinitis pigmentosa	2015-01-01	no assertion criteria provided	research