Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000322792 | SCV000343337 | uncertain significance | not provided | 2016-07-12 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000322792 | SCV002243415 | pathogenic | not provided | 2023-09-24 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Met519 amino acid residue in CNGA3. Other variant(s) that disrupt this residue have been observed in individuals with CNGA3-related conditions (PMID: 26992781, 27208204, 30682209), which suggests that this may be a clinically significant amino acid residue. 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: 236463). This missense change has been observed in individual(s) with achromatopsia and/or CNGA3-related conditions (PMID: 27208204, 30682209; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs199655686, gnomAD 0.01%). This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 519 of the CNGA3 protein (p.Met519Ile). |
Centre for Genomic Medicine, |
RCV000225371 | SCV000282569 | uncertain significance | Retinal dystrophy | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000678543 | SCV000804620 | uncertain significance | Achromatopsia 2 | 2016-09-01 | flagged submission | clinical testing | |
Clinical Genetics, |
RCV000322792 | SCV001923131 | likely pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000322792 | SCV001966725 | likely pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000322792 | SCV001979520 | likely pathogenic | not provided | no assertion criteria provided | clinical testing |