Submissions for variant NM_001297.5(CNGB1):c.232G>A (p.Ala78Thr)

gnomAD frequency: 0.00131  dbSNP: rs201407276

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000309330	SCV000398375	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001000923	SCV001158010	uncertain significance	Retinitis pigmentosa 45	2018-12-13	criteria provided, single submitter	clinical testing	The CNGB1 c.232G>A; p.Ala78Thr variant (rs201407276), to our knowledge, is not reported in the medical literature or gene-specific databases. The variant is described in the ClinVar database (Variation ID: 320112) and in the African population with an allele frequency of 0.4% (105/24188 alleles) in the Genome Aggregation Database. The amino acid at this position is weakly conserved and computational algorithms (PolyPhen-2, SIFT) predict this variant is tolerated. Considering available information, the clinical significance of this variant cannot be determined with certainty.
Invitae	RCV001430950	SCV001633699	likely benign	not provided	2024-01-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001430950	SCV002526302	uncertain significance	not provided	2022-06-09	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV002522881	SCV003646723	uncertain significance	Inborn genetic diseases	2021-08-17	criteria provided, single submitter	clinical testing	The c.232G>A (p.A78T) alteration is located in exon 4 (coding exon 3) of the CNGB1 gene. This alteration results from a G to A substitution at nucleotide position 232, causing the alanine (A) at amino acid position 78 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003910216	SCV004720406	likely benign	CNGB1-related disorder	2023-02-22	criteria provided, single submitter	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).