ABCC7 p.Ala1067Val
| ClinVar: |
c.3200C>T
,
p.Ala1067Val
?
, not provided
c.3199G>C , p.Ala1067Pro ? , not provided c.3200C>G , p.Ala1067Gly ? , not provided c.3200C>A , p.Ala1067Asp ? , not provided c.3199G>A , p.Ala1067Thr ? , Conflicting interpretations of pathogenicity, not provided |
| CF databases: |
c.3200C>A
,
p.Ala1067Asp
(CFTR1)
D
, This substitution involves a residue conserved among species, located in an intracellular loop, and affects the charge of the CFTR protein. It was found at the homozygous state in a patient originating from India, and having a classical severe form of CF. A1067D creates a MaeIII restriction site.
c.3199G>C , p.Ala1067Pro (CFTR1) D , The mutation was detected by DHPLC analysis and characterized by direct seqencing c.3199G>A , p.Ala1067Thr (CFTR1) ? , This child is 2 years old, carries the [delta]F508 mutation on the other chromosome, and is at this time a mild form of the disease. c.3200C>G , p.Ala1067Gly (CFTR1) ? , This change has been detected by DGGE analysis and direct sequencing in one Spanish allele c.3200C>T , p.Ala1067Val (CFTR1) ? , Ala to Val at 1067 |
| Predicted by SNAP2: | C: D (91%), D: D (95%), E: D (95%), F: D (95%), G: D (95%), H: D (95%), I: D (95%), K: D (95%), L: D (95%), M: D (95%), N: D (95%), P: D (95%), Q: D (95%), R: D (95%), S: D (91%), T: N (87%), V: D (71%), W: D (95%), Y: D (95%), |
| Predicted by PROVEAN: | C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: N, T: D, V: D, W: D, Y: D, |
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[hide] Molecular screening of the CFTR gene in men with a... Mol Hum Reprod. 2000 Dec;6(12):1063-7. Jezequel P, Dubourg C, Le Lannou D, Odent S, Le Gall JY, Blayau M, Le Treut A, David V
Molecular screening of the CFTR gene in men with anomalies of the vas deferens: identification of three novel mutations.
Mol Hum Reprod. 2000 Dec;6(12):1063-7., [PMID:11101688]
Abstract [show]
Many studies have shown that congenital absence of the vas deferens (CAVD) is a genital cystic fibrosis transmembrane conductance regulator (CFTR)-mediated phenotype, with a broad spectrum of abnormalities causing male infertility. The genotype of these patients includes mutations in the CFTR gene, e.g. DeltaDeltaF508, R117H and the T5 allele; all of which are commonly found in CAVD. In this study we have screened the entirety of CFTR gene in 47 males with anomalies of the vas deferens: 37 cases of congenital bilateral absence of the vas deferens, three cases of congenital unilateral absence of the vas deferens and seven cases of obstructive azoospermia with hypoplastic vas deferens. Among the 94 chromosomes studied, 65 mutations, of which three are novel (2789+2insA, L1227S, 4428insGA), were identified. The majority of patients (63.8%) had two detectable CFTR gene mutations. Furthermore, high frequencies of the DeltaDeltaF508 mutation (44.7%), the T5 allele (36.2%) and R117H mutation (19.1%) were observed.
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No. Sentence Comment
60 Tworegions (1, 2, 5, 6a, 6b, 7, 10, 11, 12, 14a, 14b, 15, 16, 17a, 17b, 18, 20, 22, 23, 24) were amplified with a GC-clamp primer and six exons mutations were found in 31.9% of patients, 31.9% had one Table I. Summary of the clinical and biological findings of a population of men with congenital bilateral absence of the vas deferens (CBAVD, n ϭ 37), congenital unilateral absence of the vas deferens (CUAVD, n ϭ 3) and obstructive azoospermia (Obs A, n ϭ 7) Patient Phenotype Surgical Age Weight Height Sweat test Other clinical CFTR exploration (years) (kg) (m) (Cl- mEq/l) manifestation genotype 1 CBAVD ϩ 40 63 1.72 72 ∆F508/T5 2 CBAVD ϩ 31 66 1.76 40 L1227S/3272-26A→G 3 CBAVD ϩ 29 ∆F508/T5 4 CBAVD 29 sinusitis -/- 5 CBAVD 32 50 1.60 ∆F508/T5 6 CBAVD 35 64 1.66 ∆F508/T5 7 CBAVD ϩ 28 ∆F508/R117H 8 CBAVD ϩ 34 69 1.80 24 ∆F508/R117H 9 CBAVD ϩ 35 65 1.70 R117H/T5 10 CBAVD ϩ 32 50 1.70 31 asthma ∆F508/T5 11 CBAVD ϩ 26 left hydrocele T5/- 12 CBAVD ϩ 23 left varicocele, G551D/T5 asthma, anosmia 13 CBAVD ϩ 29 ∆F508/T5 14 CBAVD ϩ 36 63 1.64 52 ∆F508/R117H 15 CBAVD ϩ 37 60 1.76 ∆F508/T5 16 CBAVD ϩ 34 70 1.65 24 ∆F508/A1067V 17 CBAVD 35 61 1.73 42 ∆F508/R117H 18 CBAVD 25 72 1.82 86 2183AA→G/T5 19 CBAVD 28 88 1.76 7 -/- 20 CBAVD ϩ 29 ∆F508/T5 21 CBAVD 31 48 epididymite -/- 22 CBAVD 28 ∆F508/T5 23 CBAVD ϩ 32 68 1.76 36 flatulence ∆F508/R1070W 24 CBAVD ϩ 31 64 1.76 39 R1162X/T5 25 CBAVD 30 17 asthma R117H/L375F 26 CBAVD ϩ 36 62 1.70 ∆F508/R1070W 27 CBAVD 30 6 -/- 28 CBAVD 35 85 1.70 R1070W/- 29 CBAVD 39 bronchectasis -/- 30 CBAVD ϩ 29 ∆F508/- 31 CBAVD 31 bronchectasis, -/- deafness 32 CBAVD ϩ 26 asthma, otitis -/- 33 CBAVD ϩ 28 allergy -/- 34 CBAVD 37 36 R117H/- 35 CBAVD 33 -/- 36 CBAVD ϩ 30 64 1.68 R117H/T5 37 CBAVD ϩ 37 71 1.78 31 pancreatitis, 621ϩ1G→T/I980K alcoholism 38 CUAVD 43 62 1.68 40 allergy G542X/R1070W 39 CUAVD ϩ 35 allergy ∆F508/R117H 40 CUAVD ϩ 34 hydrocele L375F/G551D 41 Obs A ϩ 32 26 T5/- 42 Obs A 23 60 sinusitis ∆F508/2789ϩ2insA 43 Obs A ϩ 25 80 sinusitis, chronic ∆F508/4428insGA 44 Obs A ϩ 30 bronchitis -/- anosmia 45 Obs A 29 50 -/- 46 Obs A 29 75 1.77 ∆F508/T5 47 Obs A ϩ 30 82 1.66 -/- mutation and the T5 allele, 10.7% had only one mutation and clinical palpation.
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ABCC7 p.Ala1067Val 11101688:60:1305
status: NEW73 This mutation creates a stop codon 43 nucleotides 26 ∆F508/R1070W (TG)10T9/(TG)10T7 downstream leading to the deletion of 33 C-terminus amino 16 ∆F508/A1067V (TG)10T9/(TG)10T7 acids of the CFTR protein including the TRL-COOH domain.42 ∆F508/2789ϩ2insA (TG)10T9/(TG)10T7 43 ∆F508/4428insGA (TG)10T9/(TG)11T7 This highly conserved proteic site is a perfect match for the 25 R117H/L375F (TG)10T7/(TG)10T7 binding consensus domain of the Naϩ-Hϩ exchanger regulatory 38 G542X/R1070W (TG)10T9/(TG)11T7 factor (NHE-RF), a cytoplasmic phosphoprotein that may play40 L375F/G551D (TG)10T7/(TG)10T7 37 621ϩ1G→T/I980K (TG)10T9/(TG)10T9 an important regulatory role in CFTR function (Wang et al., 2 L1227S/3272-26A→G (TG)10T9/(TG)12T7 1998).
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ABCC7 p.Ala1067Val 11101688:73:165
status: NEW[hide] A novel computational and structural analysis of n... Genomic Med. 2008 Jan;2(1-2):23-32. Epub 2008 May 14. George Priya Doss C, Rajasekaran R, Sudandiradoss C, Ramanathan K, Purohit R, Sethumadhavan R
A novel computational and structural analysis of nsSNPs in CFTR gene.
Genomic Med. 2008 Jan;2(1-2):23-32. Epub 2008 May 14., [PMID:18716917]
Abstract [show]
Single Nucleotide Polymorphisms (SNPs) are being intensively studied to understand the biological basis of complex traits and diseases. The Genetics of human phenotype variation could be understood by knowing the functions of SNPs. In this study using computational methods, we analyzed the genetic variations that can alter the expression and function of the CFTR gene responsible candidate for causing cystic fibrosis. We applied an evolutionary perspective to screen the SNPs using a sequence homology-based SIFT tool, which suggested that 17 nsSNPs (44%) were found to be deleterious. The structure-based approach PolyPhen server suggested that 26 nsSNPS (66%) may disrupt protein function and structure. The PupaSuite tool predicted the phenotypic effect of SNPs on the structure and function of the affected protein. Structure analysis was carried out with the major mutation that occurred in the native protein coded by CFTR gene, and which is at amino acid position F508C for nsSNP with id (rs1800093). The amino acid residues in the native and mutant modeled protein were further analyzed for solvent accessibility, secondary structure and stabilizing residues to check the stability of the proteins. The SNPs were further subjected to iHAP analysis to identify htSNPs, and we report potential candidates for future studies on CFTR mutations.
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No. Sentence Comment
125 The nsSNPs which were predicted to be Table 1 List of nsSNPs that were predicted to be deleterious by SIFT and PolyPhen SNPs ID Alleles AA change Tolerance index PSIC rs1800072 G/A V11C 1.00 0.150 rs1800073 C/T R31C 0.18 2.288 rs1800074 A/T D44V 0.01 2.532 rs1800076 G/A R75Q 0.03 1.754 rs1800078 T/C L138P 0.01 2.192 rs35516286 T/C I148T 0.41 1.743 rs1800079 G/A R170H 0.05 1.968 rs1800080 A/G S182G 0.03 1.699 rs1800086 C/G T351S 0.30 1.600 rs1800087 A/C Q353H 0.03 2.093 rs4727853 C/A N417K 1.00 0.015 rs11531593 C/A F433L 0.65 0.694 rs1800089 C/T L467F 0.15 1.568 rs213950 G/A V470M 0.17 1.432 rs1800092 C/A/G I506M 0.00 1.574 rs1801178 A/G I507V 0.38 0.314 rs1800093 T/G F508C 0.00 3.031 rs35032490 A/G K532E 1.00 1.525 rs1800097 G/A V562I 0.13 0.345 rs41290377 G/C G576A 0.33 1.262 rs766874 C/T S605F 0.03 2.147 rs1800099 A/G S654G 0.03 1.611 rs1800100 C/T R668C 0.01 2.654 rs1800101 T/C F693L 0.61 0.895 rs1800103 A/G I807M 0.01 1.554 rs1800106 T/C Y903H 0.52 0.183 rs1800107 G/T S909I 0.10 1.624 rs1800110 T/C L967S 0.07 1.683 rs1800111 G/C L997F 0.24 1.000 rs1800112 T/C I1027T 0.03 1.860 rs1800114 C/T A1067V 0.04 1.542 rs36210737 T/A M1101K 0.05 2.637 rs35813506 G/A R1102K 0.52 1.589 rs1800120 G/T R1162L 0.00 2.038 rs1800123 C/T T1220I 0.22 0.059 rs34911792 T/G S1235R 0.45 1.483 rs11971167 G/A D1270N 0.12 1.739 rs4148725 C/T R1453W 0.00 2.513 Highly deleterious by SIFT and damaging by PolyPhen are indicated as bold deleterious in causing an effect in the structure and function of the protein by SIFT, PolyPhen and Pupasuite correlated well with experimental studies (Tsui 1992; Ghanem et al. 1994; Bienvenu et al. 1998) (Table 3).
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ABCC7 p.Ala1067Val 18716917:125:1112
status: NEW[hide] Structural analysis of CFTR gene in congenital bil... Clin Chem. 1995 Jun;41(6 Pt 1):833-5. Jezequel P, Dorval I, Fergelot P, Chauvel B, Le Treut A, Le Gall JY, Le Lannou D, Blayau M
Structural analysis of CFTR gene in congenital bilateral absence of vas deferens.
Clin Chem. 1995 Jun;41(6 Pt 1):833-5., [PMID:7539342]
Abstract [show]
Congenital bilateral absence of the vas deferens (CBAVD) is found in most males with cystic fibrosis (CF), but this malformation can be observed without any pulmonary or digestive features. We have analyzed 13 exons of the CF gene in a cohort of 25 CBAVD patients. Among the 50 chromosomes studied, 24 mutations were identified: delta F508 (14 cases), R117H (7 cases), R1070W (2 cases), 621 + 1 G --> T (1 case), and A1067V (1 case). Except for delta F508, the most frequent mutations (R117H, R1070W) were not observed in the CF group (109 patients) studied in our laboratory. We discuss the significance of these results.
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No. Sentence Comment
45 F508I R117H F5O8/ R1O7OW F508/A1067V 621+1G-*T /?
X
ABCC7 p.Ala1067Val 7539342:45:30
status: NEW46 SF508/ SF508 SF508 / N1303K AF508/ G551D SF508 / 3272-26G--*A SF508 / 1078 delT F508/Y1092X SF508 / Ai507 F5O8 / G542X SF508 / 621+1G-T F508 / 3898 insC SF508 / 574 delA AF508 / G85E SF508 / W1282X N1303K/F311L G551D/F311L R553X I?
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ABCC7 p.Ala1067Val 7539342:46:30
status: NEW63 Among the 50 chromosomes studied, 24 mutations (48%) were identified as follows: 13 patients were heterozygous for the SF508 deletion (52%), 6 of whom were compound heterozygous for the SF508 and missense mutations such as R117H (3 cases), R1O7OW (2 cases), and a rare mutation designated as A1067V (1 case) recently identified in a CBAVD patient (12); 5 patients had only one identified mutation: R117H (4 cases) and 621+1G-`T (1 case); and 7 patients had no mutation in the 13 studied exons.
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ABCC7 p.Ala1067Val 7539342:63:292
status: NEW64 In the intron-8 splice acceptor site the 7T variant was found in all seven R117H carriers.
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ABCC7 p.Ala1067Val 7539342:64:292
status: NEW69 In addition to iF508, we have characterized four mutations: R117H, R1O7OW, 621+1G-*T, and A1067V.
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ABCC7 p.Ala1067Val 7539342:69:90
status: NEW70 In addition to iF508, we have characterized four mutations: R117H, R1O7OW, 621+1G-*T, and A1067V.
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ABCC7 p.Ala1067Val 7539342:70:90
status: NEW[hide] Obstructive azoospermia with agenesis of vas defer... Hum Reprod. 1995 Feb;10(2):338-41. Le Lannou D, Jezequel P, Blayau M, Dorval I, Lemoine P, Dabadie A, Roussey M, Le Marec B, Legall JY
Obstructive azoospermia with agenesis of vas deferens or with bronchiectasia (Young's syndrome): a genetic approach.
Hum Reprod. 1995 Feb;10(2):338-41., [PMID:7539448]
Abstract [show]
Two groups of infertile men with obstructive azoospermia were screened for cystic fibrosis (CF) gene mutations (delta F508, exons 3, 4, 7, 10, 11, 14a, 17b, 19, 20, 21). The first group was composed of 26 patients with congenital agenesis of vas deferens (CAVD). The second group was composed of 12 patients with obstructive azoospermia associated with chronic suppurating respiratory disease (Young's syndrome). Of the group with CAVD, 77% of patients showed at least one mutation in the CF transmembrane conductance regulator (CFTR) gene. The delta F508 mutation occurred most frequently (54%), and the second most frequent mutation to occur was R117H (27%). Six patients were double heterozygotes. In Young's syndrome, no CF mutations were detected. CAVD can be considered as an incomplete clinical form of CF. However, the differences observed in CF mutations between CF and CAVD suggest that they are different disorders resulting from mutations in the same gene. Young's syndrome is a very different clinical entity.
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No. Sentence Comment
43 Six patients were double heterozygotes: AF508/R117H (three cases), AF508/ R1070W (two cases), AF508/A1067V (one case).
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ABCC7 p.Ala1067Val 7539448:43:100
status: NEW50 1 z 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 Details of cystic fibrosis (CF) mutations identified congenital agenesis of vas deferens CF mutation AF5O8/ AF508/ AF508/ AF508/ AF508/ AF5O8/A1067V AF5O8/ AF508/R1070W R117H/ AF508/R1070W - AF508/ R117H/ 621 + 1 G->T7 AF508/RU7H R117H/ AF508/R117H AF5O8/ - AF508/R117H G551D/ R117H/ Respiratory disease - - asthma bronchiectasia - - asthma - - - - rhinitis - - - - - asthma - - in all patients with Sweat tests (mmol/ml of chloride) 72a 42 31 64a 24 - 30 39 17 - 6 - 36 11 31 24 - - 7 52 - - Patients with two results >60 mmol/ml were considered positive.
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ABCC7 p.Ala1067Val 7539448:50:211
status: NEW[hide] A cluster of cystic fibrosis mutations in exon 17b... J Med Genet. 1994 Sep;31(9):731-4. Mercier B, Lissens W, Novelli G, Kalaydjieva L, de Arce M, Kapranov N, Canki Klain N, Estivill X, Palacio A, Cashman S, et al.
A cluster of cystic fibrosis mutations in exon 17b of the CFTR gene: a site for rare mutations.
J Med Genet. 1994 Sep;31(9):731-4., [PMID:7529319]
Abstract [show]
Intensive screening has improved our understanding of the profile of mutations in the CFTR gene in which more than 400 mutations have been detected to date. In collaboration with several European laboratories we are involved in such analysis. We have identified 14 new mutations in exon 17b of CFTR, having analysed 780 CF chromosomes, and have compared the frequency of mutations in this exon with that of other regions of the CFTR gene. The results obtained indicate an accumulation of mutations, not only in regions encoding the two nucleotide binding folds, but also in those encoding transmembrane domains of the CFTR gene, in particular exon 17b.
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No. Sentence Comment
33 (1) HI085R, (2) 3320 ins 5, (3) R1066C, (4)R1066H, (5) A1067V, (6) 3272-16 GA, (7) F1052V, (8) R1070Q, (9) nornmal, (10) Y1092X, (11) G1069R,(12) nornial A cluster of cystic fibrosis mutations in exon I 7b of the CFTR gene: a site for rare mutations 14b, 17a, 23, 24) (table 3).
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ABCC7 p.Ala1067Val 7529319:33:55
status: NEW