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. 2018 May 24;136(7):761–769. doi: 10.1001/jamaophthalmol.2018.1621

Table 2. Disease-Causing Variants in CNGB1 and Classification in This Study.

Variant on Nucleotide Level Consequence/Variant on Protein Level Location in CNGB1 Polypeptide gnomAD Browser MAF, %a Conservation Among Different Speciesb Predictionc ACMG Scoring Source
c.413-1G>A Splice defect N-terminal GARP 0.008 NA Human Splice Finder and MaxEntScan: broken wild-type acceptor site, new acceptor site Pathogenic (Class Ic) Azam et al,15 2011
c.1312C>T p.Q438* N-terminal GARP NA NA Mutationtaster: disease causing Pathogenic (Class Ib) Present study
c.2210G>A p.R737H TD3 0.002 HsCNGB1 R, MmCNGB1 R, DrCngb1 R PolyPhen-2: probably damaging (score 0.999), SIFT: damaging (score 0.4), Mutationtaster: disease causing VUS Present study
c.2284C>T p.R762C TD4 0.001 HsCNGB1 R, MmCNGB1 R, DrCngb1 R PolyPhen-2: probably damaging (score 1.000), SIFT: damaging (score 0), Mutationtaster: disease causing VUS Azam et al,15 2011
c.2492+1G>A Splice defect Pore NA NA Human Splice Finder and MaxEntScan: broken wild-type donor site Pathogenic (Class Ib) Present study
c.2542_2543insA p.G848Efs*4 Linker pore–TD6 NA NA Mutationtaster: disease causing Pathogenic (Class Ib) Oishi et al,22 2014
c.2763C>G p.Y921* C-linker NA NA Mutationtaster: disease causing Pathogenic (Class Ib) Present study
c.2957A>T p.N986I CNBD 0.123 HsCNGB1 N, MmCNGB1 N, DrCngb1 G PolyPhen-2: probably damaging (score 0.983), SIFT: damaging (score 0), Mutationtaster: disease causing VUS Simpson et al,16 2011
c.3044_3050delGGAAATC p.G1015Vfs*4 CNBD NA NA Mutation taster: disease causing Pathogenic (Class Ib) Present study
c.3139_3142dupGTGG p.A1048Gfs*13 CNBD NA NA Mutation taster: disease causing Pathogenic (Class Ib) Hull et al,27 2017

Abbreviations: ACMG, American College of Medical Genetics and Genomics; CNBD, cyclic nucleotide–binding domain; Dr, Danio rerio; GARP, glutamic acid–rich protein; Hs, Homo sapiens; MAF, minor allele frequency; Mm, Mus musculus; TD, transmembrane domain; NA, not applicable; VUS, variant of uncertain significance.

b

Amino acid residue affected by mutation is given in 1-letter code.

c

PolyPhen-2 (http://genetics.bwh.harvard.edu/pph2/), SIFT (http://sift.jcvi.org/), and Mutationtaster (http://www.mutationtaster.org/) for prediction for missense variants and Human Splice Finder (http://www.umd.be/HSF3/) and MaxEntScan (http://genes.mit.edu/burgelab/maxent/Xmaxentscan_scoreseq.html) for prediction of splice-site variants.