Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Genomic Medicine, |
RCV000171300 | SCV000221497 | likely pathogenic | not provided | criteria provided, single submitter | research | ||
Labcorp Genetics |
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, |
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. |