ClinVar Miner

Submissions for variant NM_001298.3(CNGA3):c.829C>T (p.Arg277Cys)

gnomAD frequency: 0.00007  dbSNP: rs104893620
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Genetics Laboratory, Institute for Ophthalmic Research RCV000596449 SCV000700220 pathogenic Achromatopsia 2018-03-20 criteria provided, single submitter research
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000626801 SCV000747504 likely pathogenic Color vision defect; Macular degeneration; Photophobia 2017-01-01 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001092740 SCV001249382 pathogenic not provided 2018-05-01 criteria provided, single submitter clinical testing
Baylor Genetics RCV000010089 SCV001524042 pathogenic Achromatopsia 2 2020-07-09 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Invitae RCV001092740 SCV001591081 pathogenic not provided 2023-12-12 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 277 of the CNGA3 protein (p.Arg277Cys). This variant is present in population databases (rs104893620, gnomAD 0.02%). This missense change has been observed in individuals with achromatopsia and cone dystrophy (PMID: 11536077). ClinVar contains an entry for this variant (Variation ID: 9481). 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: 20238023). This variant disrupts the p.Arg277 amino acid residue in CNGA3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11536077, 17693388, 26992781). 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.
GeneDx RCV001092740 SCV001785648 pathogenic not provided 2022-03-14 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect as R277C impaired channel activity compared to wild type CNGA3 (Muraki-Oda et al., 2007).; 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: 20238023, 21912902, 14736794, 14757870, 15712225, 16961972, 18521937, 15743887, 21911670, 26992781, 19592100, 24049715, 18445228, 23082193, 30682209, 30653986, 30418171, 31456290, 17693388, 11536077)
Mendelics RCV000010089 SCV002518728 pathogenic Achromatopsia 2 2022-05-04 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000010089 SCV002782956 pathogenic Achromatopsia 2 2022-02-25 criteria provided, single submitter clinical testing
OMIM RCV000010089 SCV000030310 pathogenic Achromatopsia 2 2001-10-01 no assertion criteria provided literature only
Sharon lab, Hadassah-Hebrew University Medical Center RCV000596449 SCV001161007 pathogenic Achromatopsia 2019-06-23 no assertion criteria provided research
Clinical Genetics, Academic Medical Center RCV001092740 SCV001920829 pathogenic not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001092740 SCV001959709 pathogenic not provided no assertion criteria provided clinical testing

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