ClinVar Miner

Submissions for variant NM_001298.3(CNGA3):c.955T>C (p.Cys319Arg)

gnomAD frequency: 0.00001  dbSNP: rs753625117
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department Of Translational Genomics (developmental Genetics Section), King Faisal Specialist Hospital & Research Centre RCV000171300 SCV000221497 likely pathogenic not provided criteria provided, single submitter research
Invitae RCV000171300 SCV001218424 pathogenic not provided 2022-05-15 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects CNGA3 function (PMID: 25052312). 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. ClinVar contains an entry for this variant (Variation ID: 191120). This missense change has been observed in individuals with inherited retinal disease (PMID: 25052312, 26355662). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs753625117, gnomAD 0.01%). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 319 of the CNGA3 protein (p.Cys319Arg).
Neuberg Centre For Genomic Medicine, NCGM RCV001823124 SCV002073213 likely pathogenic Achromatopsia 2 criteria provided, single submitter clinical testing The missense variant p.C319R in CNGA3 (NM_001298.3) has been observed previously in homozygous state in affected individuals (Shaikh RS et al, Patel N et al). The variant has been submitted to ClinVar as Pathogenic/Likely Pathogenic. The p.C319R variant is observed in 4/30,616 (0.0131%) alleles from individuals of South Asian background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The p.C319R missense variant is predicted to be damaging by both SIFT and PolyPhen2. The cysteine residue at codon 319 of CNGA3 is conserved in all mammalian species. The nucleotide c.955 in CNGA3 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic.

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