Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Genetics Laboratory, |
RCV000597637 | SCV000700221 | likely pathogenic | Achromatopsia | 2018-03-20 | criteria provided, single submitter | research | |
Invitae | RCV001066140 | SCV001231139 | uncertain significance | not provided | 2022-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 290 of the CNGA3 protein (p.Arg290His). This variant is present in population databases (rs199837807, gnomAD 0.03%). This missense change has been observed in individual(s) with achromatopsia (PMID: 30418171). ClinVar contains an entry for this variant (Variation ID: 503561). 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on CNGA3 function (PMID: 30418171). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Prevention |
RCV003403409 | SCV004105573 | uncertain significance | CNGA3-related condition | 2023-09-26 | criteria provided, single submitter | clinical testing | The CNGA3 c.869G>A variant is predicted to result in the amino acid substitution p.Arg290His. This variant was reported together with homozygous pathogenic variant in CNGB3 gene in an individual with retinopathy (Burkard et al. 2018. PubMed ID: 30418171). Functional study of this variant expressed heterologously showed that this variant results in normal functional protein with lower affinity for CNGB3 which in summary suggests there is no convincing evidence of pathogenicity of this variant at this time (Burkard et al. 2018. PubMed ID: 30418171). This variant was also observed in large exome study in a healthy individual and was assessed as likely pathogenic carrier variant (Table S1, Capalbo et al 2019. PubMed ID: 31589614). This variant is reported in 0.029% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-99012502-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |