Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Medical Genetics and Applied Genomics, |
RCV001268815 | SCV001448004 | pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001268815 | SCV003524670 | pathogenic | not provided | 2022-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 329 of the CNGA3 protein (p.Gly329Cys). For these reasons, this variant has been classified as Pathogenic. 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: 635157). This missense change has been observed in individuals with CNGA3-related conditions (PMID: 21778272, 30682209, 30711023, 31456290; Invitae). This variant is not present in population databases (gnomAD no frequency). |
3billion | RCV005253118 | SCV005906195 | likely pathogenic | Achromatopsia 2 | 2024-03-21 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v4.0.0 dataset. Predicted Consequence/Location: Missense variant In silico tool predictions suggest damaging effect of the variant on gene or gene product [REVEL: 0.97 (>=0.6, sensitivity 0.68 and specificity 0.92); 3Cnet: 0.96 (>=0.6, sensitivity 0.72 and precision 0.9)]. Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000635157 /PMID: 21778272 /3billion dataset). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV005253118 | SCV006072121 | pathogenic | Achromatopsia 2 | 2025-03-19 | criteria provided, single submitter | clinical testing | Variant summary: CNGA3 c.985G>T (p.Gly329Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251486 control chromosomes (gnomAD). c.985G>T has been reported in the literature in multiple individuals affected with Achromatopsia 2 (e.g. Zelinger_2015). These data indicate that the variant is very likely to be associated with disease. The following publication has been ascertained in the context of this evaluation (PMID: 25616768). ClinVar contains an entry for this variant (Variation ID: 635157). Based on the evidence outlined above, the variant was classified as pathogenic. |
Molecular Genetics Laboratory, |
RCV000786010 | SCV000924650 | pathogenic | Achromatopsia | 2017-12-13 | no assertion criteria provided | research | |
Sharon lab, |
RCV000786010 | SCV001161011 | pathogenic | Achromatopsia | 2019-06-23 | no assertion criteria provided | research |