ABCMdb

ABCC7 p.Phe693Leu

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Publications

PMID: 10970190 [PubMed] Boyne J et al: "Many deltaF508 heterozygote neonates with transient hypertrypsinaemia have a second, mild CFTR mutation."

No. Sentence Comment

538 These have been reported in patients with presenting phenotypes ranging from "cystic fibrosis" to oligospermia, but there have been too few cases Table 2 Compound heterozygotes detected Domain and mutation type Genotype Exon 1st IRT 2nd IRT Transmembrane, missense F508/P67L 3 129 34* F508/R117H 4 110 21* F508/R117H 4 84 34 F508/R117H 4 95 39 F508/R117H 4 104 40 F508/R117H 4 146 41 F508/R117H 4 104 48* F508/R117H 4 120 53 F508/R117H 4 111 54 F508/R117H 4 175 72* F508/R117L 4 129 70 F508/L967S 15 122 15 F508/F1052V 17b 189 29 F508/R1066H 17b 94 18 Transmembrane, nonsense F508/R75X 3 86 26 F508/R75X 3 171 27 F508/R851X 14a 112 76 Regulatory, missense F508/F693L 13 109 29 Alternate splice site F508/3849+10KB C→T i19 99 26* F508/3849+10KB C→T i19 112 36* None of these samples had the IVS8-5T variant sequence. Login to comment
543 The missense mutation F693L is located in the regulatory domain of CFTR and was first identified in a young girl with F508 on her other allele who was diagnosed with pancreatic insuYcient cystic fibrosis.26 Three subjects had nonsense mutations which are normally associated with severe disease as they introduce a stop codon, leading to truncated, usually inactive, CFTR protein being transcribed. Login to comment

PMID: 11504857 [PubMed] Chen JM et al: "A combined analysis of the cystic fibrosis transmembrane conductance regulator: implications for structure and disease models."

No. Sentence Comment

590 Taking advantage of the previously redefined R domain, a systemic evaluation of the missense mutations occurring in this region was produced, and as a result, some of these mutations, such as F693L, V754M, and T760M, were identified as being likely to represent neutral polymorphisms (Chen, Scotet, and Ferec 2000). Login to comment

PMID: 12167682 [PubMed] Groman JD et al: "Variant cystic fibrosis phenotypes in the absence of CFTR mutations."

No. Sentence Comment

71 MUTATION IDENTIFIED BY SCREENING FOR COMMON MUTATIONS MUTATION IDENTIFIED BY DNA SEQUENCING NO. OF PATIENTS ∆F508 5T* 3 ∆F508 D1152H 2 ∆F508 2789+2insA 2 ∆F508 R117C 2 ∆F508 D110H 1 ∆F508 2789+5G→A 1 ∆F508 P205S 1 ∆F508 L967S 1 ∆F508 I1027T 1 ∆F508 L206W 1 ∆F508 T1053I and 5T 1 ∆F508 V920M and 5T 1 ∆F508 R1070W 1 ∆F508 D579G 1 ∆F508 P67L 1 ∆F508 2811G→T†‡ 1 G85E F191V† 1 R117H G103X and 5T 1 I148T I556V 1 G542X R1162L 1 W1282X D1152H 1 None L138ins and 3272-26 A→G 1 None G463D† and 5T 1 None F693L and 5T 1 ∆F508 None 6 G551D None 1 W1282X None 1 None 5T 4 None 2307insA 1 None L997F 1 None V520I 1 None None 30 in Subject II-2 in Family 1. Login to comment

PMID: 15354332 [PubMed] Monaghan KG et al: "Preconception and prenatal cystic fibrosis carrier screening of African Americans reveals unanticipated frequencies for specific mutations."

No. Sentence Comment

44 Three additional sequence changes, F693L (TTG), Q98R, and P140S(C3T), were incidentally detected by heteroduplex analysis while screening for ACOG/ ACMG CF mutations not included in the test kit used during the time of screening. Login to comment
46 F693L (TTG) and P140S (C3T) are variants of unknown clinical significance. Login to comment
51 R117H has been previously reported at an increased frequency among individuals undergoing carrier screening compared to those with a diagnosis of cystic fibrosis.8 An unexpected result was the lack of 3120ϩ1G3A carriers, although 4 were expected given that this mutation accounts for Ϸ12% of the CF muta- Table 1 Summary of carrier screening results using various methods employed between December 2001 and September 2003 OLA v2.0, heteroduplex analysis (exons 4 and 13) and RFLP analysis (3120ϩ1G3A) OLA v3.0 INNO-LiPA Total screened 818 1274 97 No. of carriers identified 16 14 3 Observed carrier frequency 1/51 1/81 Mutations identified ⌬F508 (6), G622D (3), R117H/7T (3), I148T (3199del6 negative), Q98R, 1898ϩ1G3A, and G551Da ⌬F508 (14), R117H/7T, R553X, and G551D a In addition, 2 persons were positive for F693L (TTG) and 1 was positive for P140S (C3T at 550); both are variants of unknown clinical significance. Login to comment
57 Two mutations, G622D and Q98R, and two variants of unknown clinical significance, F693L (TTG) and P140S (C3T), which are not part of the recommended CF screening panel, were incidentally detected while using heteroduplex analysis to screen for ACOG/ACMG recommended mutations (Table 2). Login to comment
64 This is the case with F693L (TTG), which is currently classified as a CF mutation, reported on one Hispanic CF chromosome in a patient who also had the 5T allele (whether the two mutations were in-trans versus in-cis was not reported).9 However, a different base substitution in the same codon resulting in the same amino acid substitution, F693L (CTT), originally reported as a CF mutation,10 was also reported as a polymorphism.9 This mutation was later shown by functional studies to not affect the CFTR chloride channel activity or protein maturation.11 Therefore, the significance of finding F693 (TTG) in our African American population is not clear. Login to comment

PMID: 18716917 [PubMed] George Priya Doss C et al: "A novel computational and structural analysis of nsSNPs in CFTR gene."

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). Login to comment

PMID: 19017867 [PubMed] Mutesa L et al: "Genetic analysis of Rwandan patients with cystic fibrosis-like symptoms: identification of novel cystic fibrosis transmembrane conductance regulator and epithelial sodium channel gene variants."

No. Sentence Comment

51 We found 14 CFTR variants (Table 2), as follows: two known mutations (p.F693L and c.3120 ϩ 1GϾA); a novel p.A204T missense mutation; and nine sequence polymorphisms; and two previously uncharacterized intronic nucleotide changes, c.3272-32T Ͼ C in the intron 17a and c.4575 ϩ 2GϾA in the 3Ј-untranslated region (UTR). Login to comment
61 The p.F693L mutation was identified in the following two patients: a 13-year-old boy (patient P004) with recurrent respiratory infections, lung colonization by P aeruginosa, GI symptoms, failure to thrive, Table 1-Characteristics of 60 Patients With CF-Like Symptoms Variables Patients (n ϭ 60) % Age, yr Range 2-14 Mean Ϯ SD 5.8 Ϯ 1.7 Sex Male 33 55 Female 27 45 Phenotype Chronic lung disease 39 65 GI symptoms 41 68 Pancreatic insufficiency 19 32 Failure to thrive 23 38 PEM 52 87 Diabetes mellitus 4 7 Nasal polyps 3 5 Sweat chloride test results Positive (Ͼ 60 mmol/L) 37 62 Borderline (40-60 mol/L) 11 18 Normal (Ͻ 40 mmol/L) 9 15 Test not performed 3 5 www.chestjournal.org CHEST / 135 / 5 / MAY, 2009 1235 (c) 2009 American College of Chest Physicians at University of North Carolina on August 8, diabetes mellitus, and PEM; and a 9-year-old girl (patient P038) with mild pulmonary symptoms, GI symptoms, and severe PEM. Login to comment
73 The p.V573I ENaC variant was found in the patient who was heterozygous for the c.3120 ϩ 1GϾA CFTR mutation in combination with the TG12T7 variant, while the p.V348M ENaC mutation was observed in a patient with the p.F693L CFTR mutation. Login to comment
75 The silent polymorphism p.T577T was found in a patient with a p.F693L CFTR mutation, whereas the c.72TϾC was detected in the patient with the novel p.A204T CFTR mutation. Login to comment
91 Table 3-Comparison of Clinical Findings in Five Patients With Identified CFTR and ENaC Mutants* Patient/Sex/Age, yr Phenotype Sweat Test Value, mmol/L CFTR Genotype (͓TG͔mTn) Genotype ENaC Genotype (␣, beta, and ␥ Subunits) P004/M/13 LD, PA, GI, PEM 94 p.F693L/- (TG)10T7/(TG)11T9 p.V348M (beta) p.S212S† (␥) P038/F/9 LD, SA, GI, PEM 124 p.F693L/- (TG)10T7/(TG)10T9 p.T577T (beta) p.G442V† (beta) P007/F/7 LD, PA, GI, PEM 85 c.3120 ϩ 1GϾA/- (TG)11T7/(TG)12T7 p.V573I (␣) p.G442V† (beta) P029/M/2 GI, PI, FT, PEM 77 c.4575 ϩ 2GϾA‡/- (TG)10T7/(TG)11T5 c.1473 ϩ 28CϾT (beta) c.1176 ϩ 30GϾC (␥) P041/F/4 LD, PEM 113 p.A204T/- (TG)10T7/(TG)10T7 c.72 TϾC (␣ 5Ј UTR) p.G442V† (beta) *Tn ϭ poly-T tract; TGm ϭ poly-TG loci; LD ϭ lung disease; PA ϭ P aeruginosa lung colonization; FT ϭ failure to thrive; DM ϭ diabetes mellitus; PI ϭ pancreatic insufficiency; SA ϭ Staphylococcus aureus lung colonization; F ϭ female; M ϭ male. Login to comment
95 CFTR Allele Variants, % (n ϭ 120) p.F693L TϾG at 2211 13 PheϾLeu at 693 2 1.67 c.3120 ϩ 1GϾA GϾA at 3120 ϩ 1 Intron 16 Splicing mutation 1 0.83 p.A204T* GϾA at 742 6a AlaϾThr at 742 1 0.83 c.4575 ϩ 2GϾA GϾA at 4575 ϩ 2 3Ј UTR 1 0.83 p.T854T TϾG at 2694 14a Sequence variation 52 43.33 p.Q1463Q GϾA at 4521 24 Sequence variation 14 11.7 p.M470V AϾG at 1540 10 Sequence variation 13 10.83 c.1898 ϩ 152TϾA TϾA at 1898 ϩ 152 12 Sequence variation 9 7.5 p.P1290P AϾG at 4002 20 Sequence variation 6 5 c.1001 ϩ 11CϾT CϾT at 1001 ϩ 11 Intron 6b Sequence variation 5 4.17 p.E527E AϾG at 1713 10 Sequence variation 3 2.5 c.2752 - 15CϾG CϾG at 2752 - 15 Intron 14a Sequence variation 3 2.5 c.3041 - 71AϾG GϾC at 3041 - 71 Intron 15 Sequence variation 2 1.67 c.3272 - 32TϾC TϾC at 3072 - 32 Intron17a 1 0.83 *Identified novel missense mutation. Login to comment
101 The identified mutations were as follows: (1) a c.3120 ϩ 1GϾA CFTR mutation, frequently observed in African patients and responsible for a splicing defect4; and (2) a p.F693L CFTR missense mutation in two patients with CF-like severe symptoms including recurrent lung disease (the same amino acid change at the same residue has been previously reported23 in an Italian CF patient with severe symptoms; moreover, these two patients carried SCNN1B mutations) [Table 3]; (3) a TG11T5 variant, which can be associated with mild CF signs; and (4) a novel p.A204T CFTR mutation. Login to comment
129 For instance, the two patients with a p.F693L CFTR mutation carried the p.V348M or p.T577T SCNN1B mutation, which were not detected in the control group. Login to comment
47 We found 14 CFTR variants (Table 2), as follows: two known mutations (p.F693L and c.3120 ϩ 1GϾA); a novel p.A204T missense mutation; and nine sequence polymorphisms; and two previously uncharacterized intronic nucleotide changes, c.3272-32T Ͼ C in the intron 17a and c.4575 ϩ 2GϾA in the 3Ј-untranslated region (UTR). Login to comment
57 The p.F693L mutation was identified in the following two patients: a 13-year-old boy (patient P004) with recurrent respiratory infections, lung colonization by P aeruginosa, GI symptoms, failure to thrive, Table 1-Characteristics of 60 Patients With CF-Like Symptoms Variables Patients (n ϭ 60) % Age, yr Range 2-14 Mean Ϯ SD 5.8 Ϯ 1.7 Sex Male 33 55 Female 27 45 Phenotype Chronic lung disease 39 65 GI symptoms 41 68 Pancreatic insufficiency 19 32 Failure to thrive 23 38 PEM 52 87 Diabetes mellitus 4 7 Nasal polyps 3 5 Sweat chloride test results Positive (Ͼ 60 mmol/L) 37 62 Borderline (40-60 mol/L) 11 18 Normal (Ͻ 40 mmol/L) 9 15 Test not performed 3 5 diabetes mellitus, and PEM; and a 9-year-old girl (patient P038) with mild pulmonary symptoms, GI symptoms, and severe PEM. Login to comment
69 The p.V573I ENaC variant was found in the patient who was heterozygous for the c.3120 ϩ 1GϾA CFTR mutation in combination with the TG12T7 variant, while the p.V348M ENaC mutation was observed in a patient with the p.F693L CFTR mutation. Login to comment
71 The silent polymorphism p.T577T was found in a patient with a p.F693L CFTR mutation, whereas the c.72TϾC was detected in the patient with the novel p.A204T CFTR mutation. Login to comment
87 Table 3-Comparison of Clinical Findings in Five Patients With Identified CFTR and ENaC Mutants* Patient/Sex/Age, yr Phenotype Sweat Test Value, mmol/L CFTR Genotype (͓TG͔mTn) Genotype ENaC Genotype (␣, beta, and ␥ Subunits) P004/M/13 LD, PA, GI, PEM 94 p.F693L/- (TG)10T7/(TG)11T9 p.V348M (beta) p.S212S† (␥) P038/F/9 LD, SA, GI, PEM 124 p.F693L/- (TG)10T7/(TG)10T9 p.T577T (beta) p.G442V† (beta) P007/F/7 LD, PA, GI, PEM 85 c.3120 ϩ 1GϾA/- (TG)11T7/(TG)12T7 p.V573I (␣) p.G442V† (beta) P029/M/2 GI, PI, FT, PEM 77 c.4575 ϩ 2GϾA‡/- (TG)10T7/(TG)11T5 c.1473 ϩ 28CϾT (beta) c.1176 ϩ 30GϾC (␥) P041/F/4 LD, PEM 113 p.A204T/- (TG)10T7/(TG)10T7 c.72 TϾC (␣ 5Ј UTR) p.G442V† (beta) *Tn ϭ poly-T tract; TGm ϭ poly-TG loci; LD ϭ lung disease; PA ϭ P aeruginosa lung colonization; FT ϭ failure to thrive; DM ϭ diabetes mellitus; PI ϭ pancreatic insufficiency; SA ϭ Staphylococcus aureus lung colonization; F ϭ female; M ϭ male. Login to comment
97 The identified mutations were as follows: (1) a c.3120 ϩ 1GϾA CFTR mutation, frequently observed in African patients and responsible for a splicing defect4; and (2) a p.F693L CFTR missense mutation in two patients with CF-like severe symptoms including recurrent lung disease (the same amino acid change at the same residue has been previously reported23 in an Italian CF patient with severe symptoms; moreover, these two patients carried SCNN1B mutations) [Table 3]; (3) a TG11T5 variant, which can be associated with mild CF signs; and (4) a novel p.A204T CFTR mutation. Login to comment
125 For instance, the two patients with a p.F693L CFTR mutation carried the p.V348M or p.T577T SCNN1B mutation, which were not detected in the control group. Login to comment

PMID: 9736778 [PubMed] Vankeerberghen A et al: "Characterization of 19 disease-associated missense mutations in the regulatory domain of the cystic fibrosis transmembrane conductance regulator."

No. Sentence Comment

49 Since then, it was found that the F693L mutation is a polymorphism (14,15) and that the I807M polymorphism is associated with congenital bilateral absence of the vas deferens (CBAVD) (our unpublished data). Login to comment
68 Primers used for mutagenesis Primer Sequence I601F (a1933t) 5'-CTA ACA AAA CTA GGT TTT TGG TCA CTT C-3' L610S (t1961c) 5'-CTA AAA TGG AAC ATT CAA AGA AAG CTG-3' A613T (g1969a) 5'-CAT TTA AAG AAA ACT GAC AAA ATA TTA-3' D614G (a1973g) 5'-CAT TTA AAG AAA GCT GGC AAA ATA TTA A-3' I618T (t1985c) 5'-GAC AAA ATA TTA ACT TTG CAT GAA GG-3' L619S (t1988c) 5'-GAC AAA ATA TTA ATT TCG CAT GAA GGT-3' H620P (a1991c) 5'-CAA AAT ATT AAT TTT GCC TGA AGG TAG C-3' H620Q (t1992g) 5'-AAT ATT AAT TTT GCA GGA AGG TAG CAG-3' G622D (g1997a) 5'-TTG CAT GAA GAT AGC AGC TAT TTT TAT G-3' G628R (g2014c) 5'-GCA GCT ATT TTT ATC GGA CAT TTT C-3' L633P (t2030c) 5'-CAT TTT CAG AAC CCC AAA ATC TAC AGC-3' D648V (a2075t) 5'-CTC ATG GGA TGT GTT TCT TTC GAC C-3' T665S (a2125t) 5'-CAA TCC TAA CTG AGT CCT TAC ACC G-3' F693L (t2209c) 5'-CAG ACT GGA GAG CTT GGG GAA AAA AG-3' R766M (g2429t) 5'-GCA CGA AGG ATG CAG TCT GTC CTG-3' R792G (c2506g) 5'-CAG CAT CCA CAG GAA AAG TGT CAC TG-3' A800G (c2531g) 5'-CTG GCC CCT CAG GGA AAC TTG ACT G-3' I807M (a2553g) 5'-CTG AAC TGG ATA TGT ATT CAA GAA GG-3' E822K (g2596a) 5'-GGC TTG GAA ATA AGT AAA GAA ATT AAC G-3' E826K (g2608a) 5'-GAA GAA ATT AAC AAA GAA GAC TTA AAG-3' Selection primer BstBI 5'-CTC TGG GGT CCG GAA TGA CCG AC-3' Two primers were used for each mutagenesis reaction. Login to comment
77 Mutations detected in patients (I601F, L610S, A613T, D614G, I618T, L619S, H620P, H620Q, D622G, G628R, L633P, T665S, F693L, K698R, V754M, R766M, R792G, A800G, I807M, E822K and E826K) are indicated in bold and underlined, the PKA phosphorylation sites by an arrow and the two acidic domains are boxed. Login to comment
85 The remainder (G622D, D648V, F693L, R766M and I807M) did not significantly affect chloride transport ability when compared with wild-type CFTR channels. Login to comment
87 Maturation pattern of RD mutations and their associated phenotype found in patients with the indicated genotype (when the mutation is associated with CF, only the pancreas status is given) Mutation A-form B-form C-form Clinical data Genotype Phenotype Reference I601F + + - I601F/G542X PS M. Schwarz, personal communication L610S + + - Unknown Unknown A613T + + - Unknown Unknown D614G + + - D614G/unknown PI 14 I618T + + - I618T/dF508 PS G.R. Cutting, personal communication L619S + + - L619S/unknown PI B. Tümmler, personal communication H620P + + - H620P/R1158X PS M. Schwarz, personal communication H620Q + + + H620Q/dF508 PI T. Dörk, personal communication G622D + + + G622D/unknown Oligospermia J. Zielenski, personal communication G628R + + - Unknown Unknown L633P + + - L633P/3659delC M. Schwarz, personal communication D648V + + + D648V/3849+10kb C/T PI C. Ferec, personal communication T665S + + + Unknown Unknown F693L + + + F693L/W1282X Healthy C. Ferec; CF Genetic Analysis Consortium R766M + + + R766M/R792G CBAVD D. Glavac, personal communication R792G + + + R766M/R792G CBAVD D. Glavac, personal communication A800G + + + A800G/unknown CBAVD 34 I807M + + + I807M/unknown CBAVD Our observation E822K + + + E822K/unknown PI 35 E826K + + + E826K/unknown Thoracic sarcoidosis C. Bombieri, personal communication +, the protein matures up to that form; -, the protein does not reach the respective maturation step. Login to comment
123 Mutations that did not affect maturation (H620Q, G622D, D648V, T665S, F693L, R766M, R792G, A800G, I807M, E822K and E826K) were subsequently analysedat theelectrophysiologi- cal level. Login to comment
131 The remaining mutations (D648V, T665S, F693L, R766M, I807M and E826K) caused no significant alterations in intrinsic chloride channel activity. Login to comment
132 F693L turned out to be a polymorphism (15), thereby explaining its normal function. Login to comment

PMID: 15858154 [PubMed] Schrijver I et al: "Diagnostic testing by CFTR gene mutation analysis in a large group of Hispanics: novel mutations and assessment of a population-specific mutation spectrum."

No. Sentence Comment

98 Spectrum of CFTR Sequence Variants in 257 Hispanic Patients Who Underwent Diagnostic DNA Testing for CF Mutations in 257 patients Allele counts of each mutation % of variant alleles (183) % of all alleles tested (514) ACMG/ACOG recommended 25 mutation panel* DeltaF508 53 28.96 10.31 G542X 7 3.83 1.36 R334W 2 1.09 0.39 R553X 2 1.09 0.39 DeltaI507 1 0.55 0.19 1717 - 1 GϾA 1 0.55 0.19 3120 ϩ 1 GϾA 1 0.55 0.19 7 different mutations 67 36.61 13.04 All mutations included ACMG/ACOG 1248 ϩ 1 GϾA 1 0.55 0.19 1249 - 29delAT 1 0.55 0.19 1288insTA1288insTA 1 0.55 0.19 1341 ϩ 80 GϾA1341 ϩ 80 GϾA 1 0.55 0.19 1429del71429del7 1 0.55 0.19 1525 - 42 GϾA1525 - 42 GϾA 1 0.55 0.19 1717 - 1 GϾA 1 0.55 0.19 1717 - 8 GϾA 2 1.09 0.39 1811 ϩ 1 GϾA1811 ϩ 1 GϾA 1 0.55 0.19 2055del9-ϾA 3 1.64 0.58 2105-2117del13insAGAAA 1 0.55 0.19 2215insG 1 0.55 0.19 2585delT2585delT 1 0.55 0.19 2752 - 6 TϾC 1 0.55 0.19 296 ϩ 28 AϾG 1 0.55 0.19 3120 ϩ 1 GϾ A 1 0.55 0.19 3271 ϩ 8 AϾG3271 ϩ 8 AϾG 1 0.55 0.19 3271delGG 1 0.55 0.19 3272 - 26 AϾG 2 1.09 0.39 3876delA 2 1.09 0.39 4016insT 1 0.55 0.19 406 - 1 GϾA 6 3.28 1.17 406 - 6 TϾC 1 0.55 0.19 4374 ϩ 13 A ϾG 1 0.55 0.19 663delT 1 0.55 0.19 874insTACA874insTACA 1 0.55 0.19 A1009T 2 1.09 0.39 A559T 1 0.55 0.19 D1152H 1 0.55 0.19 D1270N 3 1.64 0.58 D1445N 2 1.09 0.39 D836Y 1 0.55 0.19 DeltaF311 1 0.55 0.19 DeltaF508 53 28.96 10.31 DeltaI507 1 0.55 0.19 E116K 2 1.09 0.39 E585X 1 0.55 0.19 E588VE588V 2 1.09 0.39 E831X 1 0.55 0.19 F311L 1 0.55 0.19 F693L 1 0.55 0.19 G1244E 1 0.55 0.19 G542X 7 3.83 1.36 G576A 1 0.55 0.19 H199Y 3 1.64 0.58 I1027T 3 1.64 0.58 I285FI285F 1 0.55 0.19 L206W 3 1.64 0.58 L320V 1 0.55 0.19 L967S 1 0.55 0.19 L997F 3 1.64 0.58 P1372LP1372L 1 0.55 0.19 P205S 1 0.55 0.19 P439SP439S 1 0.55 0.19 Q1313X 1 0.55 0.19 Q890X 2 1.09 0.39 Q98R 1 0.55 0.19 R1066C 1 0.55 0.19 R1066H 1 0.55 0.19 (Table continues) missense variant, I1027T (3212TϾC), in exon 17a.25 Family studies have not been performed to identify which allele carries two mutations. Login to comment
186 Table 3. Continued CFTR mutations Alleles Relative mutation frequency (%) (of 317) G567A 1 Ͻ1 S573C 1 Ͻ1 E585X 1 Ͻ1 T604S 1 Ͻ1 F693L 1 Ͻ1 V754 mol/L 1 Ͻ1 2108delA 1 Ͻ1 2184delA 1 Ͻ1 2215insG 1 Ͻ1 2585delT 1 Ͻ1 2752 - 6TϾC 1 Ͻ1 E831X 1 Ͻ1 D836Y 1 Ͻ1 Y913X 1 Ͻ1 S945L 1 Ͻ1 L967S 1 Ͻ1 3171delC 1 Ͻ1 3199del6 1 Ͻ1 3271 ϩ 8AϾG 1 Ͻ1 R1066H 1 Ͻ1 R1070W 1 Ͻ1 Y1092X 1 Ͻ1 W1098C 1 Ͻ1 3500 - 2AϾT 1 Ͻ1 4016insT 1 Ͻ1 4374 ϩ 13AϾG 1 Ͻ1 D1152H 1 Ͻ1 R1158X 1 Ͻ1 R1162X 1 Ͻ1 W1282X 1 Ͻ1 N1303K 1 Ͻ1 Q1313X 1 Ͻ1 P1372L 1 Ͻ1 R1438W 1 Ͻ1 Total 317 100 Table 3. Login to comment

PMID: 11001817 [PubMed] Chen JM et al: "Definition of a "functional R domain" of the cystic fibrosis transmembrane conductance regulator."

No. Sentence Comment

45 For example, F693L, V754M, T760M, and A800G may be assigned as neutral polymorphisms. Login to comment
46 Indeed, F693L was considered to be a neutral polymorphism due to its presence in healthy subjects (unpublished data) and this was confirmed by functional analysis (8). Login to comment

PMID: 14685937 [PubMed] Groman JD et al: "Variation in a repeat sequence determines whether a common variant of the cystic fibrosis transmembrane conductance regulator gene is pathogenic or benign."

No. Sentence Comment

40 Nine patients with nonclassic CF were referred from CF care centers in the United States and were confirmed to have a 5T in trans with one of the following CFTR mutations: DF508 (6), 2814insA (1), G463D (1), or F693L (1). Login to comment

PMID: 23087020 [PubMed] Rauh R et al: "A mutation in the beta-subunit of ENaC identified in a patient with cystic fibrosis-like symptoms has a gain-of-function effect."

No. Sentence Comment

377 In this context, it is of interest that the patient reported by Mutesa et al. (39) was compound heterozygous for the betaV348M mutation and a F693L-CFTR mutation. Login to comment
378 The F693L-CFTR mutation was described as a polymorphism that, compared with wild-type CFTR, did not affect channel maturation in COS1 cells or chloride transport ability in oocytes (57). Login to comment
379 Therefore, it seems unlikely that the F693L-CFTR mutation alone is sufficient to cause the disease. Login to comment