Submissions for variant NM_001298.3(CNGA3):c.847C>T (p.Arg283Trp)

gnomAD frequency: 0.00002  dbSNP: rs104893613

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000415133	SCV000492977	likely pathogenic	Monochromacy	2014-07-21	criteria provided, single submitter	clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000010082	SCV001367338	likely pathogenic	Achromatopsia 2	2019-09-12	criteria provided, single submitter	clinical testing	This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PM1,PM2,PM5,PP3,PP5.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001222182	SCV001394271	pathogenic	not provided	2024-03-07	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 283 of the CNGA3 protein (p.Arg283Trp). This variant is present in population databases (rs104893613, gnomAD 0.02%). This missense change has been observed in individual(s) with achromatopsia (PMID: 9662398, 11536077, 24504161, 25637600, 26992781). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 9474). 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 CNGA3 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects CNGA3 function (PMID: 17693388, 20238023). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV001222182	SCV001773382	pathogenic	not provided	2021-11-26	criteria provided, single submitter	clinical testing	Published functional studies demonstrate a damaging effect consistent with loss-of-function (Muraki-Oda et al., 2007; Ding et al., 2010); 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: 26992781, 31237654, 32141364, 20238023, 24504161, 9662398, 16319819, 17693388, 11536077, 30682209, 31877759, 32869108, 33562422, 32037395)
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001222182	SCV001905566	pathogenic	not provided	2021-09-15	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001222182	SCV002063881	pathogenic	not provided	2022-10-01	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000010082	SCV004041266	pathogenic	Achromatopsia 2	2023-07-08	criteria provided, single submitter	clinical testing
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004794328	SCV005071876	pathogenic	Retinal dystrophy	2023-01-01	criteria provided, single submitter	clinical testing
Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel	RCV004794328	SCV005415462	pathogenic	Retinal dystrophy	2024-05-27	criteria provided, single submitter	research
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	RCV000010082	SCV005420630	pathogenic	Achromatopsia 2	2024-10-04	criteria provided, single submitter	research	PS3,PP1,PM3,PM2,PM5,PP3
Fulgent Genetics, Fulgent Genetics	RCV000010082	SCV005663329	pathogenic	Achromatopsia 2	2024-04-02	criteria provided, single submitter	clinical testing
OMIM	RCV000010082	SCV000030303	pathogenic	Achromatopsia 2	2001-10-01	no assertion criteria provided	literature only
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000010082	SCV000804621	pathogenic	Achromatopsia 2	2016-09-01	no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001222182	SCV001956988	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001222182	SCV001966736	pathogenic	not provided		no assertion criteria provided	clinical testing