ClinVar Miner

Submissions for variant NM_001298.3(CNGA3):c.1114C>T (p.Pro372Ser)

gnomAD frequency: 0.00001  dbSNP: rs1464167194
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001060342 SCV001225023 pathogenic not provided 2024-01-30 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 372 of the CNGA3 protein (p.Pro372Ser). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with achromatopsia (PMID: 11536077, 20506298, 28559085, 29053603). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is also known as c.1060C>T (p.P354S). ClinVar contains an entry for this variant (Variation ID: 812281). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects CNGA3 function (PMID: 17693388, 20506298). For these reasons, this variant has been classified as Pathogenic.
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital RCV001270466 SCV005420632 pathogenic Achromatopsia 2 2024-10-04 criteria provided, single submitter research PS3,PP1,PM1,PM2,PM3-moderate,PP3
Sharon lab, Hadassah-Hebrew University Medical Center RCV001002966 SCV001161013 pathogenic Achromatopsia 2019-06-23 no assertion criteria provided research
Laboratory of Genetics in Ophthalmology, Institut Imagine RCV001270466 SCV001450756 likely pathogenic Achromatopsia 2 no assertion criteria provided research
PreventionGenetics, part of Exact Sciences RCV004754675 SCV005346864 pathogenic CNGA3-related disorder 2024-05-03 no assertion criteria provided clinical testing The CNGA3 c.1114C>T variant is predicted to result in the amino acid substitution p.Pro372Ser. This variant has been reported many times in individuals with achromatopsia (see for examples Wissinger et al. 2001. PubMed ID: 11536077; Table S1, Stone et al. 2017. PubMed ID: 28559085; Table S2, Sharon et al. 2019. PubMed ID: 31456290; 2020. PubMed ID: 31725702). Functional studies using protein expression in cell culture have found that the p.Pro372Ser substitution reduces cell surface expression and activity (Koeppen et al. 2010. PubMed ID: 20506298; Muraki-Oda et al. 2007. PubMed ID: 17693388). This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD. Given the evidence, we interpret this variant as pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.