ClinVar Miner

Submissions for variant NM_001298.3(CNGA3):c.1557G>A (p.Met519Ile)

gnomAD frequency: 0.00004  dbSNP: rs199655686
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) 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, Manchester, Central Manchester University Hospitals RCV000225371 SCV000282569 uncertain significance Retinal dystrophy no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000678543 SCV000804620 uncertain significance Achromatopsia 2 2016-09-01 flagged submission clinical testing
Clinical Genetics, Academic Medical Center RCV000322792 SCV001923131 likely pathogenic not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000322792 SCV001966725 likely pathogenic not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000322792 SCV001979520 likely pathogenic not provided no assertion criteria provided clinical testing

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