Submissions for variant NM_001298.3(CNGA3):c.827A>G (p.Asn276Ser)

dbSNP: rs199474697

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001543590	SCV001762266	likely pathogenic	not provided	2021-06-17	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001543590	SCV004292633	likely pathogenic	not provided	2024-04-25	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 276 of the CNGA3 protein (p.Asn276Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of achromatopsia (PMID: 21912902, 35456423, 35754085). ClinVar contains an entry for this variant (Variation ID: 156335). 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: 35456423). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000144419	SCV000189474	not provided	Achromatopsia 2		no assertion provided	not provided