ClinVar Miner

Submissions for variant NM_001298.3(CNGA3):c.1597G>C (p.Asp533His)

dbSNP: rs775332304
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV001074601 SCV001240192 pathogenic Retinal dystrophy 2019-01-16 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000325405 SCV001398141 pathogenic not provided 2022-09-13 criteria provided, single submitter clinical testing 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: 282547). This missense change has been observed in individual(s) with clinical features of cone-rod dystrophy (PMID: 24903488; 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 (rs775332304, gnomAD 0.003%). This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 533 of the CNGA3 protein (p.Asp533His).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004689700 SCV005184804 likely pathogenic Achromatopsia 2 2024-05-13 criteria provided, single submitter clinical testing Variant summary: CNGA3 c.1597G>C (p.Asp533His) results in a non-conservative amino acid change located in the Cyclic nucleotide-binding domain (IPR000595) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251220 control chromosomes. c.1597G>C has been reported in the literature in at least 1 individual affected with cone-rod dystrophy (example, Sun_2020). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence demonstrating this variant was associated with complete loss of channel activity (example, Solaki_2023). The following publications have been ascertained in the context of this evaluation (PMID: 37689994, 32913385). ClinVar contains an entry for this variant (Variation ID: 282547). Based on the evidence outlined above, the variant was classified as likely pathogenic.
Fulgent Genetics, Fulgent Genetics RCV004689700 SCV005663340 likely pathogenic Achromatopsia 2 2024-05-17 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000325405 SCV000334074 uncertain significance not provided 2018-03-12 flagged submission clinical testing

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