ClinVar Miner

Submissions for variant NM_001298.3(CNGA3):c.668G>A (p.Arg223Gln)

gnomAD frequency: 0.00002  dbSNP: rs762668060
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV001073423 SCV001238964 pathogenic Retinal dystrophy 2019-02-01 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001092739 SCV001249381 pathogenic not provided 2016-12-01 criteria provided, single submitter clinical testing
Invitae RCV001092739 SCV001417281 pathogenic not provided 2024-01-23 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 223 of the CNGA3 protein (p.Arg223Gln). This variant is present in population databases (rs762668060, gnomAD 0.02%). This missense change has been observed in individuals with achromatopsia, cone-rod dystrophy, or Bull's eye maculopathy (PMID: 24504161, 24903488, 25283059, 26992781). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 865874). 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%. This variant disrupts the p.Arg223 amino acid residue in CNGA3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11536077, 24504161, 24903488, 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 RCV001092739 SCV003919261 likely pathogenic not provided 2022-10-18 criteria provided, single submitter clinical testing 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: 24504161, 24903488, 25283059, 26992781, 31980526, 32531858)

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