Submissions for variant NM_001298.3(CNGA3):c.542A>G (p.Tyr181Cys)

dbSNP: rs1692740329

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001384600	SCV001584157	pathogenic	not provided	2020-07-22	criteria provided, single submitter	clinical testing	This variant has been reported to affect CNGA3 protein function (PMID:17693388,15980212). This sequence change replaces tyrosine with cysteine at codon 181 of the CNGA3 protein (p.Tyr181Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. This variant has been observed in individual(s) with clinical features of achromatopsia (PMID: 31237654, 11536077, Invitae). This variant is not present in population databases (ExAC no frequency).
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004815519	SCV005071875	pathogenic	Retinal dystrophy	2023-01-01	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV001384600	SCV001918728	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001384600	SCV001975719	likely pathogenic	not provided		no assertion criteria provided	clinical testing