NM_001298.3(CNGA3):c.668G>A (p.Arg223Gln) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Jan 6, 2025
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001092739.33

Allele description [Variation Report for NM_001298.3(CNGA3):c.668G>A (p.Arg223Gln)]

NM_001298.3(CNGA3):c.668G>A (p.Arg223Gln)

Gene:

CNGA3:cyclic nucleotide gated channel subunit alpha 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q11.2

Genomic location:

Preferred name:

NM_001298.3(CNGA3):c.668G>A (p.Arg223Gln)

HGVS:

NC_000002.12:g.98391965G>A
NG_009097.1:g.50811G>A
NM_001079878.2:c.614G>A
NM_001298.3:c.668G>AMANE SELECT
NP_001073347.1:p.Arg205Gln
NP_001289.1:p.Arg223Gln
NC_000002.11:g.99008428G>A
NM_001298.2:c.668G>A

Protein change:

R205Q

Links:

dbSNP: rs762668060

NCBI 1000 Genomes Browser:

rs762668060

Molecular consequence:

NM_001079878.2:c.614G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001298.3:c.668G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001249381	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Dec 1, 2016)	germline	clinical testing	Citation Link,
SCV001417281	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 6, 2025)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 25283059, 11536077, 24504161, 24903488, 26992781, 28492532
SCV003919261	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Oct 18, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001249381

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Dec 1, 2016)

germline

clinical testing

Citation Link,

SCV001417281

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 6, 2025)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV003919261

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Oct 18, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Quantitative fundus autofluorescence distinguishes ABCA4-associated and non-ABCA4-associated bull's-eye maculopathy.

Duncker T, Tsang SH, Lee W, Zernant J, Allikmets R, Delori FC, Sparrow JR.

Ophthalmology. 2015 Feb;122(2):345-55. doi: 10.1016/j.ophtha.2014.08.017. Epub 2014 Oct 3.

PubMed [citation]

PMID:: 25283059
PMCID:: PMC4306619

CNGA3 mutations in hereditary cone photoreceptor disorders.

Wissinger B, Gamer D, Jägle H, Giorda R, Marx T, Mayer S, Tippmann S, Broghammer M, Jurklies B, Rosenberg T, Jacobson SG, Sener EC, Tatlipinar S, Hoyng CB, Castellan C, Bitoun P, Andreasson S, Rudolph G, Kellner U, Lorenz B, Wolff G, Verellen-Dumoulin C, et al.

Am J Hum Genet. 2001 Oct;69(4):722-37. Epub 2001 Aug 30.

PubMed [citation]

PMID:: 11536077
PMCID:: PMC1226059

See all PubMed Citations (6)

Details of each submission

From CeGaT Center for Human Genetics Tuebingen, SCV001249381.30

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001417281.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 223 of the CNGA3 protein (p.Arg223Gln). This variant is present in population databases (rs762668060, gnomAD 0.02%). This missense change has been observed in individuals with achromatopsia, cone-rod dystrophy, or Bull's eye maculopathy (PMID: 24504161, 24903488, 25283059, 26992781). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 865874). 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) indicates that this missense variant is expected to disrupt CNGA3 protein function with a positive predictive value of 95%. This variant disrupts the p.Arg223 amino acid residue in CNGA3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11536077, 24504161, 24903488, 26992781). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV003919261.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24504161, 24903488, 25283059, 26992781, 31980526, 32531858)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 25, 2025

ClinVar

Relating variation to medicine