Submissions for variant NM_003835.4(RGS9):c.895T>C (p.Trp299Arg)

gnomAD frequency: 0.00019  dbSNP: rs121908449

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001052039	SCV001216229	pathogenic	not provided	2023-09-21	criteria provided, single submitter	clinical testing	This missense change has been observed in individuals with bradyopsia and/or cone dysfunction (PMID: 14702087, 17826834, 19818506). It has also been observed to segregate with disease in related individuals. This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 299 of the RGS9 protein (p.Trp299Arg). This variant is present in population databases (rs121908449, gnomAD 0.02%). ClinVar contains an entry for this variant (Variation ID: 5862). 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 not expected to disrupt RGS9 protein function. Experimental studies have shown that this missense change affects RGS9 function (PMID: 14702087). For these reasons, this variant has been classified as Pathogenic.
OMIM	RCV000006220	SCV000026402	drug response	Bradyopsia	2004-01-01	no assertion criteria provided	literature only
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000787876	SCV000926892	pathogenic	Leber congenital amaurosis	2018-04-01	no assertion criteria provided	research
Clinical Genetics, Academic Medical Center	RCV001052039	SCV001918194	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001052039	SCV001957206	likely pathogenic	not provided		no assertion criteria provided	clinical testing