Submissions for variant NM_001297.5(CNGB1):c.878G>A (p.Ser293Asn)

gnomAD frequency: 0.00105  dbSNP: rs146170855

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000723993	SCV000225819	uncertain significance	not provided	2014-08-25	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000320799	SCV000398361	uncertain significance	Retinitis pigmentosa	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000723993	SCV000568882	uncertain significance	not provided	2015-12-03	criteria provided, single submitter	clinical testing	The S293N variant in the CNGB1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The S293N variant was not observed at any significant frequency in approximately 6200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S293N variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved; Asparagine is seen in one species. In silico analysis predicts this variant likely does not alter the protein structure/function. We interpret S293N as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000723993	SCV001673821	likely benign	not provided	2025-01-21	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004975306	SCV005556915	uncertain significance	Inborn genetic diseases	2024-08-02	criteria provided, single submitter	clinical testing	The c.878G>A (p.S293N) alteration is located in exon 13 (coding exon 12) of the CNGB1 gene. This alteration results from a G to A substitution at nucleotide position 878, causing the serine (S) at amino acid position 293 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004816261	SCV005069338	uncertain significance	Optic atrophy	2022-01-01	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004757970	SCV005351773	likely benign	CNGB1-related disorder	2024-07-25	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).