ABCC7 p.Ala209Ser
| ClinVar: |
c.627A>G
,
p.Ala209=
?
, not provided
c.625G>T , p.Ala209Ser ? , not provided |
| CF databases: |
c.625G>T
,
p.Ala209Ser
(CFTR1)
?
, CF patient.
|
| Predicted by SNAP2: | C: N (57%), D: D (80%), E: D (80%), F: D (75%), G: D (59%), H: D (80%), I: N (93%), K: D (80%), L: N (66%), M: N (78%), N: D (66%), P: D (80%), Q: D (71%), R: D (80%), S: D (53%), T: N (87%), V: N (93%), W: D (85%), Y: D (80%), |
| Predicted by PROVEAN: | C: N, D: D, E: N, F: N, G: N, H: D, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: D, Y: N, |
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[hide] Complete and rapid scanning of the cystic fibrosis... Hum Genet. 2001 Apr;108(4):290-8. Le Marechal C, Audrezet MP, Quere I, Raguenes O, Langonne S, Ferec C
Complete and rapid scanning of the cystic fibrosis transmembrane conductance regulator (CFTR) gene by denaturing high-performance liquid chromatography (D-HPLC): major implications for genetic counselling.
Hum Genet. 2001 Apr;108(4):290-8., [PMID:11379874]
Abstract [show]
More than 900 mutations and more than 200 different polymorphisms have now been reported in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Ten years after the cloning of the CFTR gene, the complete scanning of the 27 exons to identify known and novel mutations remains challenging. Rapid accurate identification of mutated alleles is important for prenatal diagnosis, for cascade screening in families at risk of cystic fibrosis (CF) and for understanding the correlation between genotype and phenotype. In this study, we report the successful use of denaturing ion-pair reverse-phase high performance liquid chromatography (D-HPLC) to analyse rapidly the complete coding sequence of the CFTR gene. With 27 pairs of polymerase chain reaction primers, we optimised the temperature conditions required for the analysis of each amplicon and validated thetest conditions on samples from a panel of 1552 CF patients who came from France and other European countries and who had mutations and polymorphisms located in the various melting domains of the gene. D-HPLC identified 415 mutated alleles previously characterised by denaturing gradient gel electrophoresis and DNA sequencing, plus 74 novel mutations reported here. This new technique for screening DNA for sequence variation was extremely accurate (it identified 100% of the CFTR alleles tested so far) and rapid (the complete CFTR gene could be analysed in less than a week). Our approach should reduce the number of untyped CF alleles in populations and thus decrease the residual risk in couples at risk of CF. This technique may be important not only for CF,but also for many other genes with a high frequency of point mutations at a variety of sites.
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No. Sentence Comment
114 At 56°C, the profiles of ∆F508 and M470V are identical 295 Table 2 Novel nucleotide changes identified in the CFTR gene and detected by D-HPLC Exon/ intron Mutant name Nucleic acid change Amino acid change Effect on amino acid sequence Patient 1 185+1 G to T G to T at 185+1 Splicing CF patient 2 186 - 13 C to G C to G at 186-13 Silent CF patient 2 211 Del G Deletion of G at 211 Frameshift CF patient 2 237 Ins A Insertion A at 237 Frameshift CF patient 2 296+2 T to C 296+2 T to C Splicing CF patient 3 W 57 X2 G to A at 303 Trp to Stop at 57 (TGG to TGA) Nonsense CF patient 3 306 InsA Insertion of A at 306 Frameshift CF patient 3 306 Ins C Insertion of C at 306 Frameshift CF patient 3 W 79 X G to A at 368 Trp to Stop at 79 (TGG to TAG) Nonsense CF patient 4 A 96 E C to A at 419 Ala to Glu at 96 (GCA to GAA) Missense CF patient 4 L 127 X T to G at 512 Nonsense CF patient 4 541 Del CTCC Deletion of CTCC at 541 Leu to Stop at 127 (TTA to TGA) Frameshift CF patient 5 L 165 S T to C at 626 Leu to Ser at 165 (TTA to TCA) Missense CF patient 5 R 170 C C to T at 640 Arg to Cys at 170 (CGT to TGT) Missense Control 6a L 206 F G to T at 750 Leu to Phe at 206 (TTG to TTT) Missense CF patient 6a A 209 S G to T at 757 Ala to Ser at 209 (GCA toTCA) Missense CF patient 6a A 209 A A to G at 759 Ala to Ala at 209 (GCA to GCG) Silent CF patient 6a C 225 X T to A at 807 Cys to Stop at 225 (TGT to TGA) Nonsense CF patient 6a G 241 R G to A at 852 Gly to Arg at 241 (GGG to AGG) Missense CF patient 6b 905 Del G Deletion of Gat 905 Frameshift CF patient 7 A 309 A C to G at 1059 Ala to Ala at 309 (GCC to GCG) Silent Control 7 V 322 M G to A at 1096 Val to Met at 322 (GTG to ATG) Silent CF patient 7 R 334 Q G to A at 1133 Arg to Gln at 334 (CGG toCAG) Missense Control 7 Q 353 H A to C at 1191 Gln to His at 353 (CAA to CAC) Missense CF patient 7 1248+1 G to C G to C at 1248+1 Splicing CF patient 8 L 383 L G to A at 1281 Leu to Leu at 383 (TTG to TTA) Silent Control 8 W 401 X G to A at 1334 Trp to Stop at 401 (TGG to TAG) Nonsense CF patient 8 E 403 D G to C at 1341 Glu to Asp at 403 (GAG to CAG) Missense CF patient 9 1367 Del C Frameshift CF patient 10 1525 - 2 A to G Deletion of C at 1367 Splicing CF patient 10 G 480 G T to C at 1572 Gly to Gly at 480 (GGT to GGC) Silent CF patient 10 1576 Ins T Insertion of T at 1576 Frameshift CF patient 10 H 484 R A to G at 1583 His to Arg at 484 (CAC to CGC) Missense Neonatal hypertrypsinaemia 10 I506 V A to G at 1648 Ileto Val at 506 (ATC to GTC) Silent Control 11 1717 - 19 T to C T to C at 1717-19 Splicing ?
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ABCC7 p.Ala209Ser 11379874:114:1235
status: NEW[hide] Prospective analysis of cystic fibrosis transmembr... Chest. 2006 Oct;130(4):995-1002. Ziedalski TM, Kao PN, Henig NR, Jacobs SS, Ruoss SJ
Prospective analysis of cystic fibrosis transmembrane regulator mutations in adults with bronchiectasis or pulmonary nontuberculous mycobacterial infection.
Chest. 2006 Oct;130(4):995-1002., [PMID:17035430]
Abstract [show]
BACKGROUND: Bronchiectasis and pulmonary infection with nontuberculous mycobacteria (NTM) may be associated with disease-causing mutations in the cystic fibrosis transmembrane regulator (CFTR). METHODS: Fifty adult patients at Stanford University Medical Center with a diagnosis of bronchiectasis and/or pulmonary NTM infection were prospectively characterized by sweat chloride measurement, comprehensive mutational analysis of CFTR, and sputum culture results. RESULTS: A de novo diagnosis of cystic fibrosis (CF) was established in 10 patients (20%). Patients with CF were more likely than those without CF to have mucus plugging seen on chest high-resolution CT, and women with a CF diagnosis were thinner, with a significantly lower mean body mass index than the non-CF subjects. Thirty CFTR mutations were identified in 24 patients (50% prevalence). Sweat chloride concentration was elevated > 60 mEq/dL (diagnostic of CF) in seven patients (14%), and from 40 to 60 mEq/dL in eight patients (16%). The frequency of CFTR mutations was elevated above that expected in the general population: heterozygous DeltaF508 (12% vs 3%), R75Q (14% vs 1%), and intron 8 5T (17% vs 5 to 10%). Other known CFTR mutations identified were V456A, G542X, R668C, I1027T, D1152, R1162L, W1282X, and L183I. Three novel CFTR mutations were identified: A394V, F650L, and C1344S. CONCLUSIONS: Mutations in CFTR that alter RNA splicing and/or functional chloride conductance are common in this population, and are likely to contribute to the susceptibility and pathogenesis of adult bronchiectasis and pulmonary NTM infection. Careful clinical evaluation for disease cause should be undertaken in this clinical context.
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No. Sentence Comment
113 In contrast to Table 3-Subjects With Normal Sweat Chloride Concentrations (< 40 mEq/dL)* Patient No. Age, yr Sex Bronch NTM† Other Infection‡ CFTR Mutations M470V Alleles IVS8 PolyT Sweat Chloride, mEq/dL 19 40 F Y Mab 1 7T/7T 19 20 41 F Y MAC 1 7T/7T 20 21 74 F Y MAC, Mgo Asp, Noc ⌬F508 1 7T/9T 22 22 28 M Y MAC L183I 1 7T/7T 23 23 49 F Y MAC 1 7T/7T 25 24 58 M Y MAC, Mfo 1 5T/7T 25 25 76 F Y MAC SA A394V 2 5T/9T 26 26 79 F Y MAC 1 7T/7T 27 27 58 F Y MAC R75Q 1 7T/7T 28 28 78 F Y MAC PA 1 7T/9T 31 29 64 F Y MAC 1 5T/9T 31 30 57 F Y MAC, Mxe R75Q 2 7T/7T 34 31 81 F Y MAC, Mmu R668C 1 7T/7T 34 32 82 F Y N PA F650L 1 5T/9T 33 33 69 F Y MAC, Mch, Mab PA ⌬F508 0 7T/9T 35 34 81 F Y MAC C1344S 2 7T/7T 38 35 72 F Y MAC R75Q 2 7T/7T 38 36 55 M Y N ⌬F508 1 7T/7T 21 37 61 F Y N 0 7T/9T 20 38 42 F Y N 1 9T/9T 21 39 50 M Y N PA, SA, Asp 1 5T/7T 22 40 71 M Y N 2 7T/7T 23 41 83 F Y N 2 7T/7T 23 42 46 M Y N 2 7T/7T 25 43 49 F Y N R75Q 2 7T/7T 33 44 48 F Y N PA R75Q 2 9T/9T 35 45 76 F Y N R1162L 1 7T/7T 35 46 67 M Y N A209S 0 9T/9T 36 47 46 F Y N 1 7T/7T 36 48 63 F N MAC 1 9T/9T § 49 60 F N MAC 1 7T/7T 31 50 40 F Y Mab 1 7T/7T 19 *See Tables 1 and 2 for expansion of abbreviations.
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ABCC7 p.Ala209Ser 17035430:113:1052
status: NEW[hide] Increased risk of idiopathic chronic pancreatitis ... Hum Mutat. 2005 Oct;26(4):303-7. Cohn JA, Neoptolemos JP, Feng J, Yan J, Jiang Z, Greenhalf W, McFaul C, Mountford R, Sommer SS
Increased risk of idiopathic chronic pancreatitis in cystic fibrosis carriers.
Hum Mutat. 2005 Oct;26(4):303-7., [PMID:16134171]
Abstract [show]
Cystic fibrosis (CF) is a recessive disease caused by mutations of the CF transmembrane conductance regulator (CFTR) gene. The risk of idiopathic chronic pancreatitis (ICP) is increased in individuals who have CFTR genotypes containing a CF-causing mutation plus a second pathogenic allele. It is unknown whether the risk of ICP is increased in CF carriers who have one CF-causing mutation plus one normal allele. In this study, 52 sporadic cases of ICP were ascertained through the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer. Individuals with pathogenic cationic trypsinogen mutations were excluded. DNA was comprehensively tested for CFTR mutations using a robotically enhanced, multiplexed, and highly redundant form of single-strand conformation polymorphism (SSCP) analysis followed by DNA sequencing. Fifteen subjects had a total of 18 pathogenic CFTR alleles. Eight subjects had common CF-causing mutations. This group included seven CF carriers in whom the second CFTR allele was normal (4.3 times the expected frequency, P=0.0002). Three subjects had compound heterozygotes genotypes containing two pathogenic alleles (31 times the expected frequency, P<0.0001). A variant allele of uncertain significance (p.R75Q) was detected in eight of the 52 ICP subjects and at a similar frequency (13/96) in random donors. ICP differs from other established CFTR-related conditions in that ICP risk is increased in CF carriers who have one documented normal CFTR allele. Having two CFTR mutations imparts a higher relative risk, while having only one mutation imparts a higher attributable risk.
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No. Sentence Comment
93 Abnormal CFTR Genotypes Detected in 52 Patients with ICPa Genotype categorya ] Patients Genotypes detectedb Compound heterozygotes and homozygotes 3 p.F508del / p.L967S p.D1152H / p.D1152H p.V920M / p.L967S Heterozygotes, common mutation causing classic CFa 7 p.F508del /^ ('ve subjects)c p.R560T/^ p.G542X /^ Heterozygotes, uncommon mutation causing variable phenotype 3 p.S1235R /^ p.A209S /^ p.L997F/^ Heterozygotes, common CBAVD-associated mutation 2 IVS8(5T) /^ (two subjects) a Common CF-mutations consistently cause classic CF in compound heterozygotes and homozygotes [Rosenstein and Cutting, 1998].
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ABCC7 p.Ala209Ser 16134171:93:386
status: NEW106 If p.R75Q is reclassified as an uncommon mutation causing a variable phenotype, this would change the genotype category for four subjects: one CF carrier would become a compound heterozygote (p.F508del/p.R75Q), two heterozygotes would become compound heterozygotes (p.S1235R/ p.R75Q and p.A209S/p.R75Q), and one normal genotype would become a compound heterozygote or homozygote (p.R75Q/ p.R75Q).
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ABCC7 p.Ala209Ser 16134171:106:289
status: NEW