Total submissions: 12
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Genetics Laboratory, |
RCV000596449 | SCV000700220 | pathogenic | Achromatopsia | 2018-03-20 | criteria provided, single submitter | research | |
Centre for Mendelian Genomics, |
RCV000626801 | SCV000747504 | likely pathogenic | Color vision defect; Macular degeneration; Photophobia | 2017-01-01 | criteria provided, single submitter | clinical testing | |
Ce |
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. |
Gene |
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, |
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, |
RCV000596449 | SCV001161007 | pathogenic | Achromatopsia | 2019-06-23 | no assertion criteria provided | research | |
Clinical Genetics, |
RCV001092740 | SCV001920829 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV001092740 | SCV001959709 | pathogenic | not provided | no assertion criteria provided | clinical testing |