ABCMdb

ABCC7 p.Ser50Pro

ClinVar:	c.148T>C , p.Ser50Pro ? , not provided c.149C>A , p.Ser50Tyr ? , not provided
CF databases:	c.148T>C , p.Ser50Pro (CFTR1) D , Abnormal pattern in SSCA exon 2 was observed for I50T. Direct sequence of the sample allowed us to detect this new mutation. This mutation was observed in a Spanish man with CBAVD, carrying DE115 in the other chromosome. c.149C>A , p.Ser50Tyr (CFTR1) D , New missense mutation detected in exon 2 of the CFTR gene. Transversion C to A at position 281 of the CFTR gene was detected in a CBAVD patient by heteroduplex-MDE analysis using the following exon 2 specific primers: 21-5, 5'-CCAAATCTGTATGGAGACCA-3' and 2i-3s, 5'-AGCCACCATACTTGGCTCCT-3'. The change leads to a substitution of tyrosine for serine at position 50 of the polypeptide (S50Y). Except the [delta]F508 mutation and two variants (1898+152A and 1001+11T) no other change was detected by heteroduplex analysis of all CFTR exons in this patient. The S50Y allele was found once among 126 chromosomes from CBAVD patients.
Predicted by SNAP2:	A: N (57%), C: D (63%), D: D (85%), E: D (80%), F: D (85%), G: N (57%), H: D (85%), I: D (85%), K: D (80%), L: D (80%), M: D (85%), N: D (71%), P: D (80%), Q: D (71%), R: D (80%), T: D (63%), V: D (71%), W: D (91%), Y: N (61%),
Predicted by PROVEAN:	A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, T: N, V: N, W: D, Y: N,

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[hide] Heterogeneity for mutations in the CFTR gene and c... Hum Reprod. 2000 Jul;15(7):1476-83. Casals T, Bassas L, Egozcue S, Ramos MD, Gimenez J, Segura A, Garcia F, Carrera M, Larriba S, Sarquella J, Estivill X
Heterogeneity for mutations in the CFTR gene and clinical correlations in patients with congenital absence of the vas deferens.
Hum Reprod. 2000 Jul;15(7):1476-83., [PMID:10875853]

Abstract [show]
Congenital absence of the vas deferens (CAVD) is a heterogeneous disorder, largely due to mutations in the cystic fibrosis (CFTR) gene. Patients with unilateral absence of the vas deferens (CUAVD) and patients with CAVD in association with renal agenesis appear to have a different aetiology to those with isolated CAVD. We have studied 134 Spanish CAVD patients [110 congenital bilateral absence of the vas deferens (CBAVD) and 24 CUAVD], 16 of whom (six CBAVD, 10 CUAVD) had additional renal anomalies. Forty-two different CFTR mutations were identified, seven of them being novel. Some 45% of the CFTR mutations were specific to CAVD, and were not found in patients with cystic fibrosis or in the general Spanish population. CFTR mutations were detected in 85% of CBAVD patients and in 38% of those with CUAVD. Among those patients with renal anomalies, 31% carried one CFTR mutation. Anomalies in seminal vesicles and ejaculatory ducts were common in patients with CAVD. The prevalence of cryptorchidism and inguinal hernia appeared to be increased in CAVD patients, as well as nasal pathology and frequent respiratory infections. This study confirms the molecular heterogeneity of CFTR mutations in CAVD, and emphasizes the importance of an extensive CFTR analysis in these patients. In contrast with previous studies, this report suggests that CFTR might have a role in urogenital anomalies.

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67 The abnormally migrating fragments were characterized by sequencing with the DyeDeoxy™ chain terminator method on an variant and another mutation (S50P, 2751ϩ3A→G, A1006E I. Description of the seven novel CFTR mutations and five polymorphisms in CAVD patients Mutation Location Nucleotide Amino acid Markers haplotype changes change (T)n-8CA-17bTA-M470V S50P exon 2 280 T→C Ser → Pro 5T/7T-16-31-ND D110Y exon 4 460 G→T Asp acid → Tyr 7T-17-7-V470 L383S exon 8 1280 T→C Leu → Ser 7T-16-7-M470 H484Y exon 10 1582 C→T His → Tyr no phase-M470 2751ϩ3A→G intron 14a 2751ϩ3 A→G - 5T-16-30-ND Q890R exon 15 2801 A→G Glu → Arg 7T-16-7/29-V470 P1021S exon 17a 3193 C→T Pro → Ser 7T-17-7-M470 Polymorphisms 104C/A 5ЈUTR - 296ϩ128G/C intron 3 - 741C/T exon 6a Ile203 no change 3195A/T exon 17a Pro1021 no change 3212T/C exon 17a Ile1027 no change CAVD ϭ congenital absence of the vas deferens; ND ϭ not determined; 5ЈUTR ϭ 5Ј untranslated region. Login to comment
78 Except for the S50P mutation, which is associated to 5T and 7T alleles in CAVD patients, the other three infections. Login to comment
95 CFTR genotypes in 24 patients with congenital unilateral absenceTable III. CFTR genotypes in 110 patients with congenital bilateral absence of the vas deferens of the vas deferens Mutations IVS8-6(T) n (%)Mutations IVS8-6(T) n (%) Two CFTR mutations 62 (56) Two CFTR mutations 5 (21) ∆F508/- 5T/9T 2 (8)∆F508/- 5T/9T 17 (15) G542X/- 5T/9T 6 (5) G542X/- 5T/9T 1 3732delA/- 5T/7T 1∆F508/L206W 9T/9T 6 (5) ∆F508/D1270NϩR74W 7T/9T 3 (3) L383S/- 5T/7T 1 One CFTR mutation 4 (17)∆F508/R117H 7T/7T 1 ∆F508/P1021S 7T/9T 1 ∆F508/-a 7T/9T 1 3732delA/-a 7T/7T 1∆F508/M952T 7T/9T 1 ∆F508/D110Y 7T/9T 1 Q890R/- 7T/7T 1 -/-a 5T/7T 1∆F508/S50P 5T/9T 1 ∆F508/2751ϩ3A→G 5T/9T 1 Negative CFTR mutations 15 (62) -/- 7T/7T 10 (42)G542X/R117H 7T/9T 1 G542X/2789ϩ5G→A 7T/9T 1 -/- 7T/9T 3 (12) -/- 9T/9T 2 (8)R117H/2789ϩ5G→A 7T/7T 1 R117H/712-1G→T 7T/9T 1 R117H/∆I507 7T/7T 1 aThree carrier patients with renal agenesis. Login to comment
96 L206W/- 5T/9T 1 L206W/3121-1G→A 7T/9T 1 L206W/1949del84 7T/9T 1 transrectal ultrasonography was significantly smaller in∆E115/S50P 7T/7T 1 2869insG/R1070W 7T/7T 1 CBAVD than in CUAVD (F ϭ 8.1, P ϭ 0.005). Login to comment

[hide] N-terminal CFTR missense variants severely affect ... Hum Mutat. 2008 May;29(5):738-49. Gene GG, Llobet A, Larriba S, de Semir D, Martinez I, Escalada A, Solsona C, Casals T, Aran JM
N-terminal CFTR missense variants severely affect the behavior of the CFTR chloride channel.
Hum Mutat. 2008 May;29(5):738-49., [PMID:18306312]

Abstract [show]
Over 1,500 cystic fibrosis transmembrane conductance regulator (CFTR) gene sequence variations have been identified in patients with cystic fibrosis (CF) and related disorders involving an impaired function of the CFTR chloride channel. However, detailed structure-function analyses have only been established for a few of them. This study aimed evaluating the impact of eight N-terminus CFTR natural missense changes on channel behavior. By site-directed mutagenesis, we generated four CFTR variants in the N-terminal cytoplasmic tail (p.P5L, p.S50P, p.E60K, and p.R75Q) and four in the first transmembrane segment of membrane-spanning domain 1 (p.G85E/V, p.Y89C, and p.E92K). Immunoblot analysis revealed that p.S50P, p.E60K, p.G85E/V, and p.E92K produced only core-glycosylated proteins. Immunofluorescence and whole cell patch-clamp confirmed intracellular retention, thus reflecting a defect of CFTR folding and/or trafficking. In contrast, both p.R75Q and p.Y89C had a glycosylation pattern and a subcellular distribution comparable to the wild-type CFTR, while the percentage of mature p.P5L was considerably reduced, suggesting a major biogenesis flaw on this channel. Nevertheless, whole-cell chloride currents were recorded for all three variants. Single-channel patch-clamp analyses revealed that the channel activity of p.R75Q appeared similar to that of the wild-type CFTR, while both p.P5L and p.Y89C channels displayed abnormal gating. Overall, our results predict a major impact of the CFTR missense variants analyzed, except p.R75Q, on the CF phenotype and highlight the importance of the CFTR N-terminus on channel physiology.

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116 Moreover, some nascent/immature CFTR protein present in the ER and A B 501 E92K Y89C G85E/V P5L S50P E60K R75Q NBD1 NBD2 R FIGURE 1. Login to comment
156 Confocal images from representative xy sections taken from1of 3 independent experiments show the subcellular distribution of wild-type CFTR (WT), p.F508del mutant (F508del), and variants p.S50P (S50P), p.E60K (E60K), p.G85E (G85E), p.G85V (G85V), p.E92K (E92K), p.P5L (P5L), p.R75Q (R75Q), and p.Y89C (Y89C). Login to comment
180 B: Recordings fromvariants p.S50P (S50P), p.E60K (E60K), p.G85E (G85E), p.G85V (G85V), and p.E92K (E92K) (superimposed recordings). Login to comment
3 By site-directed mutagenesis, we generated four CFTR variants in the N-terminal cytoplasmic tail (p.P5L, p.S50P, p.E60K, and p.R75Q) and four in the first transmembrane segment of membrane-spanning domain 1 (p.G85E/V, p.Y89C, and p.E92K). Login to comment
4 Immunoblot analysis revealed that p.S50P, p.E60K, p.G85E/V, and p.E92K produced only core-glycosylated proteins. Login to comment
40 The eight CFTR variants included in this study: p.P5L, p.S50P, p.E60 K, p.R75Q, p.G85E, p.G85V, p.Y89C, and p.E92K (Fig. 1A) were generated by oligonucleotide-directed mutagenesis in pCMVCFTRNot6.2wt using the QuickChangeTM XL-Site-Directed Mutagenesis Kit (Stratagene, La Jolla, CA) according to the manufacturer`s instructions (see Supplementary Table S1 for a detailed description of the mutagenesis primers employed; available online at http://www.interscience.wiley.com/jpages/1059-7794/supp mat). Login to comment
102 RESULTS Description and Cross-Species Analysis of Natural N-Terminus CFTR Variants We chose eight naturally occurring sequence variants, four located across the N-terminal CFTR tail (p.P5L, p.S50P, p.E60K, and p.R75Q), and four within the first segment of MSD1 (p.G85E, p.G85V, p.Y89C, and p.E92 K) (Fig. 1A; Table 1). Login to comment
110 In contrast, variants p.S50P, p.E60K, p.G85E, p.G85V, and p.E92K, produced only higher mobility band B proteins suggesting that, like the p.F508del mutant, the resulting misfolded channels are retained and degraded in the cytoplasm (Fig. 2A). Login to comment
118 B: Alignment of the N-terminus (amino acids 1 to 100) of the CFTR protein derived from di¡erent species.The sequences derived from human (Homo sapiens, Gen- BankNM_000492), mouse (Mus musculus,GenBankNM_021050), Norway rat (Rattusnovergicus,GenBankNM_031506), European rabbit (Oryctolagus cuniculus, GenBank NM_001082716), cow (Bos taurus, GenBank NM_174018), sheep (Ovis aries, GenBank NM_001009781), African clawed frog (Xenopus laevis, GenBank X65256), and spiny dog'sh (Squalus acanthias, GenBank M83785) were aligned using the ClustalW multiple sequence alignment program.The amino acid residue a¡ected by each of the variants analyzed (p.P5L, p.S50P, p.E60K, p.R75Q, p.G85E, p.G85V, p.Y89C, and p.E92K) is indicated in bold. Login to comment
122 Similarly, variants p.S50P, p.E60K, p.G85V, p.G85E, and p.E92K displayed a yellow colocalization pattern clearly compatible with retention of the anomalous CFTR proteins within the intracellular compartments and no detection of PM staining (Fig. 3). Login to comment
130 Likewise, none of the five variants (p.S50P, p.E60K, p.G85E, p.G85V, and p.E92K) in which severe misprocessing was previously demonstrated (Figs. 2 and 3), was able to generate cAMP-activated currents (Fig. 4B). Login to comment
133 Genotype^Phenotype Correlation in the N-Terminal CFTR MissenseVariants Under StudyÃ Missense varianta Phenotype Second allele (number of patients)b p.P5L CF p.F508del (1), p.P205S (1) p.S50P CBAVD p.F508del (1), p.E115del (1) p.E60K CF p.G542X (1), p.I507del (1) p.R75Q HT p.F508del (3), p.E725K (1) B p.R347H (1), p.R75Q (1), n.i. (4) Br c.1584G4A (2), c.1210-7_1210-6delTT (1), n.i.(3) NT p.F508del (1) CP c.1584G4A (1), n.i. (3) MI n.i. (1) CUAVD n.i. (2) OZ n.i. (2) Normal p.R75Q (1), c.2052_2053insA (1), n.i. (1) p.G85E CF p.F508del (8), p.G542X (2), p.I507del (1), c.580-1G4T (1), p.G85E (1), c.1477_ 1478delCA (1) CBAVD p.G576A (1) HT p.L997F (1),WT (1) p.G85V CF p.F508del (2), p.G542X (2), p.Y1092X (1), c.265715G4A (1), p.A1006E, c.1210-7_1210- 6delTT (1), n.i. (1) p.Y89C CF n.i. (1)c p.E92K CF p.F508del (2), p.Q890X (1), p.L206W (1) CBAVD c.1210-7_1210-6delTT (1) ÃThe recommendations for mutation nomenclature (www.hgvs.org/mutnomen/) were used to name CFTR gene sequence variations at both the nucleotide level and the protein level. Login to comment
138 The p.S50P variant was only found in CBAVD patients [Casals et al., 2000], whereas the p.R75Q variant was described as a neutral change (CFMDB) and reported later in several CFTR-related disorders such as obstructive azoospermia [Dork et al., 1997], bronchiectasis [Casals et al., 2004b], chronic pancreatitis [Casals et al., 2004a], hypertrypsinemia [Gartner et al., 2003], as well as in the general population [Bombieri et al., 2000]. Login to comment
213 Four of the variants (p.P5L, p.S50P, p.E60 K, and p.R75Q) are localized within the cytosolic N-terminal tail, and the remaining four (p.G85E, p.G85V, p.Y89C, and p.E92K) are embedded in three positions within the first transmembrane segment (TM1) of MSD1. Login to comment
215 Accordingly, using three different approaches (immunoblotting, immunocytochemistry, and electrophysiology) we found that 5 (p.S50P, p.E60K, p.G85E, p.G85V, and p.E92K) out of the 8 variants failed to mature, showing an analogous behavior than the most common F508del mutation. Login to comment
236 Thus, all these important interactions might be perturbed by the N-tail CFTR folding mutations p.S50P and p.E60K. Login to comment
237 In the former, proline residues, such as the introduced in the p.S50P mutation, are not favored, introducing ''kinks`` in a-helices because the backbone nitrogen is not available for hydrogen bonding and because of steric constraints caused by their ring structure [Richardson and Richardson, 1989]. Login to comment
245 Indeed, similarly to the above-referred cytosolic N-terminal CFTR variants p.S50P and p.E60K, folding and/or trafficking/processing defects seem to be the major factors contributing to the abnormal p.P5L CFTR phenotype, which showed a greatly reduced expression at the PM by immunodetection. Login to comment
257 The main exception is variant p.S50P, which, despite exhibiting absence of mature CFTR protein, was merely found in two CBAVD patients [Casals et al., 2000]. Login to comment

[hide] Deletion of CFTR translation start site reveals fu... Cell Physiol Biochem. 2009;24(5-6):335-46. Epub 2009 Nov 4. Ramalho AS, Lewandowska MA, Farinha CM, Mendes F, Goncalves J, Barreto C, Harris A, Amaral MD
Deletion of CFTR translation start site reveals functional isoforms of the protein in CF patients.
Cell Physiol Biochem. 2009;24(5-6):335-46. Epub 2009 Nov 4., [PMID:19910674]

Abstract [show]
BACKGROUND/AIMS: Mutations in the CFTR gene cause Cystic Fibrosis (CF) the most common life-threatening autosomal recessive disease affecting Caucasians. We identified a CFTR mutation (c.120del23) abolishing the normal translation initiation codon, which occurs in two Portuguese CF patients. This study aims at functionally characterizing the effect of this novel mutation. METHODS: RNA and protein techniques were applied to both native tissues from CF patients and recombinant cells expressing CFTR constructs to determine whether c.120del23 allows CFTR protein production through usage of alternative internal codons, and to characterize the putative truncated CFTR form(s). RESULTS: Our data show that two shorter forms of CFTR protein are produced when the initiation translation codon is deleted indicating usage of internal initiation codons. The N-truncated CFTR generated by this mutation has decreased stability, very low processing efficiency, and drastically reduced function. Analysis of mutants of four methionine codons downstream to M1 (M82, M150, M152, M156) revealed that each of the codons M150/M152/M156 (exon 4) can mediate CFTR alternative translation. CONCLUSIONS: The CFTR N-terminus has an important role in avoiding CFTR turnover and in rendering effective its plasma membrane traffic. These data correlate well with the severe clinical phenotype of CF patients bearing the c.120del23 mutation.

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172 Altogether, these results for c.120del23-CFTR suggest an important role of the N-terminus in CFTR folding, stability and processing, which was also evidenced by other studies demonstrating that point mutations in this region - S50P; E60K; G85E/V; E92K - prevent CFTR maturation [35, 36]. Login to comment

[hide] Spectrum of mutations in the CFTR gene in cystic f... Ann Hum Genet. 2007 Mar;71(Pt 2):194-201. Alonso MJ, Heine-Suner D, Calvo M, Rosell J, Gimenez J, Ramos MD, Telleria JJ, Palacio A, Estivill X, Casals T
Spectrum of mutations in the CFTR gene in cystic fibrosis patients of Spanish ancestry.
Ann Hum Genet. 2007 Mar;71(Pt 2):194-201., [PMID:17331079]

Abstract [show]
We analyzed 1,954 Spanish cystic fibrosis (CF) alleles in order to define the molecular spectrum of mutations in the CFTR gene in Spanish CF patients. Commercial panels showed a limited detection power, leading to the identification of only 76% of alleles. Two scanning techniques, denaturing gradient gel electrophoresis (DGGE) and single strand conformation polymorphism/hetroduplex (SSCP/HD), were carried out to detect CFTR sequence changes. In addition, intragenic markers IVS8CA, IVS8-6(T)n and IVS17bTA were also analyzed. Twelve mutations showed frequencies above 1%, p.F508del being the most frequent mutation (51%). We found that eighteen mutations need to be studied to achieve a detection level of 80%. Fifty-one mutations (42%) were observed once. In total, 121 disease-causing mutations were identified, accounting for 96% (1,877 out of 1,954) of CF alleles. Specific geographic distributions for the most common mutations, p.F508del, p.G542X, c.1811 + 1.6kbA > G and c.1609delCA, were confirmed. Furthermore, two other relatively common mutations (p.V232D and c.2789 + 5G > A) showed uneven geographic distributions. This updated information on the spectrum of CF mutations in Spain will be useful for improving genetic testing, as well as to facilitate counselling in people of Spanish ancestry. In addition, this study contributes to defining the molecular spectrum of CF in Europe, and corroborates the high molecular mutation heterogeneity of Mediterranean populations.

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52 Mutation 0.46-0.35 9 c.1078delT #, p.R347P # 8 p.G85V, c.621 + 1G > T #, p.S549R (T > G) #, p.R553X #, c.3849 + 10kbC > T # 7 p.R347H #, c.1812-1G > A, p.R709X 0.30-0.10 6 p.H199Y, p.P205S, 5 p.R117H #, p.G551D #, p.W1089X, p.Y1092X, CFTR50kbdel 4 c.296 + 3insT, c.1717-1G > A #, c.1949del84, c.3849 + 1G > A 3 p.E92K, c.936delTA, c.1717-8G > A, c.1341G > A, p.A561E, c.2603delT, p.G1244E, [p.D1270N; p.R74W] 2 p.Q2X, p.P5L, CFTRdele2,3, p.S50P, p.E60K, c.405 + 1G > A, c.1677delTA, p.L558S, p.G673X, p.R851X, p.Y1014C, p.Q1100P, p.M1101K, p.D1152H, CFTRdele19, p.G1244V, p.Q1281X, p.Y1381X <0,1 1 c.124del23bp, p.Q30X, p.W57X, c.406-1G > A, p.Q98R, p.E115del, c.519delT, p.L159S, c.711 + 3A > T, p.W202X, c.875 + 1G > A, p.E278del, p.W361R, c.1215delG, p.L365P, p.A399D, c.1548delG, p.K536X, p.R560G, c.1782delA, p.L571S, [p.G576A; p.R668C], p.T582R, p.E585X, c.1898 + 1G > A, c.1898 + 3A > G, c.2051delTT, p.E692X, p.R851L, c.2711delT, c.2751 + 3A > G, c.2752-26A > G, p.D924N, p.S945L, c.3121-1G > A, p.V1008D, p.L1065R, [p.R1070W; p.R668C], [p.F1074L; 5T], p.H1085R, p.R1158X, c.3659delC #, c.3667del4, c.3737delA, c.3860ins31, c.3905insT #, c.4005 + 1G > A, p.T1299I, p.E1308X, p.Q1313X, c.4095 + 2T > A, rearrangements study (n = 4) Mutations identified in CF families with mixed European origin: c.182delT, p.L1254X, c.4010del4. Login to comment
66 For example the IVS8-6(5T) allele was detected in cis with four different mutations (p.S50P, c.2751 + 3A > G, p.A1006E and p.F1074L). Login to comment

[hide] [CFTR gene sequencing in a group of Chilean patien... Rev Chil Pediatr. 2014 Jul;85(4):448-54. doi: 10.4067/S0370-41062014000400007. Lay-Son R G, Vasquez D M, Puga Y A, Manque M P, Repetto L G
[CFTR gene sequencing in a group of Chilean patients with cystic fibrosis].
Rev Chil Pediatr. 2014 Jul;85(4):448-54. doi: 10.4067/S0370-41062014000400007., [PMID:25697318]

Abstract [show]
INTRODUCTION: Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations of the CFTR gene, in which over 1,900 different mutations have been identified. In Chile, the diagnosis panel with the 36 most common mutations detects approximately 50% of all alleles, while for Caucasians, it is nearly 90%. The objective of this study is to expand the capacity of mutational screening in Chilean patients and look for recurrent mutations at the national level. METHOD: The detection of unknown pathogenic alleles was assessed by CFTR gene sequencing in a selected group of patients from the National Cystic Fibrosis Foundation (NCFF). 39 patients, who met the CF diagnostic criteria and had only one allele identified according to the mutational panel, were studied. Massive sequencing was performed throughout the investigation and the main CFTR databases were used for analysis. RESULTS: The second pathogenic allele was identified in 16 of 39 patients of this study (41%), finding eleven different mutations that had not been reported in our population. We believe that the reason is that one of the variants had not been previously described. CONCLUSIONS: Mutations that had been described mainly in Hispanic and/or Mediterranean populations were identified. We found a variation that had not been previously reported, but not enough recurrent mutations that could explain the low rate of detection were found. Knowledge about mutations can provide appropriate genetic counseling and will be critical to evaluate the potential use of new targeted therapies for treating them.

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58 Mutaciones detectadas por secuenciaci&#f3;n masiva en cohorte de 39 pacientes chilenos con FQ portadores de un alelo desconocido Mutaci&#f3;n detectada (nomenclatura actual*) n de alelos Reporte en pacientes con FQ (no de alelos) Efecto Denominaci&#f3;n antigua c.1330_1331delAT 3 Argentina (1)a Prote&#ed;na truncada por generaci&#f3;n de cod&#f3;n de t&#e9;rmino 1460delAT c.314T>A 2 Francia (1)a Cambio de amino&#e1;cido Isoleucina por Asparagina I105N c.4046G>A 2 Italia (7)b,c , EEUU (1)d Cambio de amino&#e1;cido Glicina por Aspartato G1349D c.148T>C 2 Espa&#f1;a (2)e Cambio de amino&#e1;cido Serina por Prolina S50P c.695T>A 1 Espa&#f1;a (14)e,f , EEUU (hispanos) (5)g,h Francia (2)a , Brasil (1)i Cambio de amino&#e1;cido Valina por Aspartato V232D c.3266G>A 1 Espa&#f1;a (5)e , Brasil (2)i,j , EEUU (hispanos) (2)g , Argentina (1)k , Israel (1)l Prote&#ed;na truncada por generaci&#f3;n de cod&#f3;n de t&#e9;rmino W1089X c.1647T>G 1 Emiratos &#c1;rabes Unidos (> 30)m,n , Colombia (4)o , Israel (4)p , Argelia (2)p , Marruecos (2)q , Reino Unido (2)p , Portugal (1)p , Espa&#f1;a (1)p , Francia (1)p , Italia (1)p , Brasil (1)q , Argentina (1)q Cambio de amino&#e1;cido Serina por Arginina S549R(T- >G) c.308G>A 1 No descrita previamente Cambio de amino&#e1;cido Glicina por Glutamato G103E c.1680-1G>A 1 Espa&#f1;a (1)r Alteraci&#f3;n en splicing 1812-1G->A c.1679+1G>C 1 Francia (2)s Macedonia (1)s , Alteraci&#f3;n en splicing 1811+1G->C c.490-2A>G 1 Argentina (1)t Alteraci&#f3;n en splicing 622-2A->G FQ: Fibrosis qu&#ed;stica. Login to comment