ABCMdb

ABCC7 p.Lys411Glu

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Publications

PMID: 25492507 [PubMed] Nakano E et al: "Targeted next-generation sequencing effectively analyzed the cystic fibrosis transmembrane conductance regulator gene in pancreatitis."

No. Sentence Comment

6 We could identify 12 non-synonymous variants including three novel ones [c.A1231G (p.K411E), c.1753G[T (p.E585X) and c.2869delC (p.L957fs)] and seven synonymous variants including three novel ones in the exonic regions. Login to comment
85 Based on the presence in dbSNP137, Exome Variant Server (NHLBI GO Exome Sequencing Project, Seattle, WA, USA; URL: http://evs.gs.washington.edu/ EVS/), and the Human Genetic Variation Database, three non-synonymous variants [c.1231A[G (p.K411E), c.1753G[T (p.E585X) and c.2869delC (p.L957fs)] and three synonymous variants (c.372C[T, c.3975A[G and c.4254G[A) were novel. Login to comment
90 On average, 90.3 % of the coding region was successfully covered by C20 reads Table 2 Non-synonymous CFTR variants detected in this study Exon Non-synonymous variant Amino acid change dbSNP135 Genotype SIFT (score) PolyPhen-2 (score) Alcoholic CP (%) Idiopathic CP (%) Hereditary/ familial CP (%) 2 c.91C[T p.R31C rs1800073 CT D (0.012) PD (0.989) 0/46 (0) 3/121 (2.5) 0/26 (0) 2 c.92G[A p.R31H rs149353983 GA T (0.183) B (0.003) 0/46 (0) 1/121 (0.8) 0/26 (0) 4 c.374T[C p.I125T rs141723617 TC D (0.005) B (0.17) 0/46 (0) 2/121 (1.6) 1/26 (3.8) 10 c.1231A[G p.K411E - AG D (0.015) B (0.233) 0/46 (0) 1/121 (0.8) 0/26 (0) 11 c.1408G[A p.V470M rs213950 GA T (1) B (0) 21/46 (45.7) 65/121 (53.7) 11/26 (42.3) AA 5/46 (10.9) 19/121 (15.7) 1/26 (3.8) 12 c.1666A[G p.I556V rs75789129 AG T (0.536) B (0.334) 2/46 (4.3) 8/121 (6.6) 0/26 (0) GG 0/46 (0) 0/121 (0) 0/26 (0) 13 c.1753G[T p.E585X - GT - - 1/46 (2.2) 0/121 (0) 0/26 (0) 17 c.2869delC p.L957fs - - - 0/46 (0) 1/121 (0.8) 0/26 (0) 21 c.3468G[T p.L1156F rs139729994 GT T (0.163) PD (0.994) 2/46 (4.3) 10/121 (8.3) 2/26 (7.7) TT 1/46 (2.2) 0/121 (0) 0/26 (0) 25 c.4045G[A p.G1349S rs201686600 GA D (0) PD (1) 1/46 (2.2) 0/121 (0) 0/26 (0) 25 c.4056G[C p.Q1352H rs113857788 GC D (0) PD (1) 5/46 (10.9) 11/121 (9.1) 4/26 (15.4) CC 0/46 (0) 0/121 (0) 0/26 (0) 27 c.4357C[T p.R1453W rs4148725 CT D (0) PD (0.999) 3/46 (6.5) 6/121 (5.0) 1/26 (3.8) B benign, CP chronic pancreatitis, D damaging, PD probably damaging, T tolerated, SIFT Sorting Intolerant From Tolerant heterozygous form (Table 6). Login to comment
100 There were no significant difference for any other non-synonymous or synonymous variants detected in the exons Table 3 Comparison of the non-synonymous variant frequencies between the patients with CP and controls Amino acid change Genotype All CP (%) HGVD (%) P value (vs. HGVD) All CP Alcoholic CP Nonalcoholic CP Idiopathic CP Hereditary/ familial CP p.R31C CT 3/193 (1.6) 12/1102 (1.1) 0.48 [0.99 0.41 0.18 [0.99 p.R31H GA 1/193 (0.5) 0 - - - - - p.I125T TC 3/193 (1.6) 5/1102 (0.5) 0.11 [0.99 0.057 0.15 0.13 p.K411E AG 1/193 (0.5) 0 - - - - - p.V470M GA 97/193 (50.3) 573/1199 (47.8) 0.66 0.57 0.68 0.38 0.12 AA 25/193 (13.0) 185/1199 (15.4) p.I556V AG 10/193 (5.2) 78/1150 (6.8) 0.70 0.79 0.81 [0.99 0.45 GG 0/193 (0) 3/1150 (0.3) p.E585X GT 1/193 (0.5) 0 - - - - - p.L957fs 1/193 (0.5) 0 - - - - - p.L1156F GT 14/193 (7.3) 45/1136 (4.0) 0.04 0.06 0.07 0.11 0.30 TT 1/193 (0.5) 1/1136 (0.1) p.G1349S GA 1/193 (0.5) 4/1094 (0.4) 0.56 0.19 [0.99 [0.99 [0.99 p.Q1352H GC 20/193 (10.4) 57/1153 (4.9) 0.009 0.12 0.037 0.17 0.062 CC 0/193 (0) 1/1153 (0.1) p.R1453W CT 10/193 (5.2) 42/1144 (3.7) 0.32 0.25 0.49 0.45 [0.99 CP chronic pancreatitis, HGVB Human Genetic Variation Database P values were determined versus HGVD by the Fisher`s exact test Table 4 Synonymous variants in the exons of the CFTR gene detected in this study Exon Synonymous variant Amino acid change dbSNP135 Genotype Alcoholic CP (%) Idiopathic CP (%) Hereditary/ familial CP (%) 4 c.372C[T p.G124= - CT 0/46 (0) 1/121 (0.8) 0/26 (0) 13 c.1731C[T p.Y577= rs55928397 CT 0/46 (0) 1/121 (0.8) 0/26 (0) 15 c.2562T[G p.T854= rs1042077 TG 20/46 (43.5) 69/121 (57.0) 12/26 (46.2) GG 6/46 (13.0) 18/121 (14.9) 0/26 (0) 23 c.3723C[A p.G1241= rs185065886 CA 1/46 (2.2) 0/121 (0) 0/26 (0) 25 c.3975A[G p.R1325= - AG 0/46 (0) 1/121 (0.8) 0/26 (0) 27 c.4254G[A p.E1418= - GA 0/46 (0) 1/121 (0.8) 0/26 (0) 27 c.4389G[A p.Q1463= rs1800136 GA 1/46 (2.2) 3/121 (2.5) 0/26 (0) CP chronic pancreatitis between all patients with CP and controls (Tables 3, 5). Login to comment
114 Comprehensive analysis by targeted NGS enabled us to identify novel and Table 5 Comparison of the synonymous variant frequencies between the patients with CP and controls Synonymous variant Genotype All CP (%) HGVD (%) P value (vs. HGVD) All CP Alcoholic CP Nonalcoholic CP Idiopathic CP Hereditary/ familial CP c.C372T CT 1/193 (0.5) 0 - - - - - c.1731C[T CT 1/193 (0.5) 0 - - - - - c.2562T[G TG 101/193 (52.3) 528/1154 (45.8) 0.22 0.81 0.11 0.045 0.033 GG 24/193 (12.4) 181/1154 (15.7) c.3723C[A CA 1/193 (0.5) 3/671 (4.5) [0.99 0.23 [0.99 [0.99 [0.99 c.3975A[G AG 1/193 (0.5) 0 - - - - - c.4254G[A GA 1/193 (0.5) 0 - - - - - c.4389G[A GA 4/193 (2.1) 40/1112 (3.6) 0.48 [0.99 0.53 0.81 [0.99 AA 0/193 (0) 1/1112 (0.1) CP chronic pancreatitis, HGVD Human Genetic Variation Database P values were determined against HGVD by the Fisher`s exact test Table 6 Total CFTR sequencing results of patients carrying rare non-synonymous CFTR variants a Pancreatitis-associated mutations in the PRSS1, SPINK1, CTRC, and CPA1 genes Case# Etiology Age at onset Rare variant Additional non-synonymous variants c.1210-34TG(9_13) c.1210-12T(5_9) Mutation in other pancreatitis susceptibility genesa A1 Idiopathic 34 p.R31C/- p.R1453W/- TG11/TG11, 7T/7T - A2 Idiopathic 8 p.R31C/- - TG11/TG12, 7T/7T - A3 Idiopathic 16 p.R31C/- - TG11/TG12, 7T/7T - A4 Idiopathic 10 p.R31H/- - TG11/TG12, 7T/7T - A5 Idiopathic 16 p.I125T/- p.L1156F/- TG11/TG12, 7T/7T CTRC p.R29Q/- A6 Idiopathic 2 p.I125T/- - TG11/TG12, 7T/7T - A7 Hereditary 28 p.I125T/- p.R1453W/- TG11/TG12, 7T/7T - A8 Idiopathic 19 p.K411E/- p/L1156F/- TG11/TG12, 7T/7T - A9 Alcoholic 28 p.E585X/- p.I556V/- TG11/TG11, 7T/7T - A10 Idiopathic 21 p.L957fs/- p.Q1352H/- TG11/TG12, 7T/7T - A11 Alcoholic 40 p.G1349S/- - TG11/TG11, 7T/7T - rare variants in the CFTR gene. Login to comment
119 The pathogenic potential of another novel variant, c.1231A[G (p.K411E), is currently unknown, but the in silico analyses suggest that this variant is deleterious. Login to comment