Submissions for variant NM_001297.5(CNGB1):c.2209C>T (p.Arg737Cys)

gnomAD frequency: 0.00045  dbSNP: rs192843629

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000724483	SCV000227914	uncertain significance	not provided	2015-01-30	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000291964	SCV000398329	uncertain significance	Retinitis pigmentosa	2018-01-13	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	RCV000724483	SCV000571322	uncertain significance	not provided	2016-08-16	criteria provided, single submitter	clinical testing	The R737C variant in the CNGB1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R737C variant was not observed at any significant frequency in approximately 6100 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 R737C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R737C as a variant of uncertain significance.
Blueprint Genetics	RCV001074215	SCV001239788	uncertain significance	Retinal dystrophy	2019-04-01	criteria provided, single submitter	clinical testing
Invitae	RCV000724483	SCV001602853	likely benign	not provided	2024-01-29	criteria provided, single submitter	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000724483	SCV001957037	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000724483	SCV001965948	uncertain significance	not provided		no assertion criteria provided	clinical testing