Submissions for variant NM_001298.3(CNGA3):c.1117G>A (p.Val373Met)

gnomAD frequency: 0.00005  dbSNP: rs552553452

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Blueprint Genetics	RCV001073683	SCV001239237	uncertain significance	Retinal dystrophy	2019-08-15	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001228298	SCV001400693	pathogenic	not provided	2024-10-03	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 373 of the CNGA3 protein (p.Val373Met). This variant is present in population databases (rs552553452, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of achromatopsia (PMID: 35332618; internal data). 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: 866006). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CNGA3 protein function. For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV001073683	SCV005071190	likely pathogenic	Retinal dystrophy	2020-01-01	criteria provided, single submitter	clinical testing
Molecular Genetics Laboratory, Institute for Ophthalmic Research	RCV001729792	SCV001571293	likely pathogenic	Achromatopsia 2	2021-04-15	no assertion criteria provided	research