Submissions for variant NM_001298.3(CNGA3):c.1642G>A (p.Gly548Arg)

gnomAD frequency: 0.00001  dbSNP: rs781227859

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001238057	SCV001410852	pathogenic	not provided	2024-02-26	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 548 of the CNGA3 protein (p.Gly548Arg). This variant is present in population databases (rs781227859, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of achromatopsia (PMID: 14757870, 24148654, 25616768, 25637600, 28159970). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 812283). 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%. For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV003329356	SCV004036170	pathogenic	Achromatopsia 2	2023-09-27	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV003329356	SCV005663342	pathogenic	Achromatopsia 2	2024-01-23	criteria provided, single submitter	clinical testing
Sharon lab, Hadassah-Hebrew University Medical Center	RCV001002971	SCV001161019	likely pathogenic	Achromatopsia	2019-06-23	no assertion criteria provided	research