ClinVar Miner

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

gnomAD frequency: 0.00002  dbSNP: rs104893613
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Total submissions: 11
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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.
Invitae RCV001222182 SCV001394271 pathogenic not provided 2024-01-23 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
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 flagged submission 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

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