ABCC7 p.Gly241Arg
| ClinVar: |
c.721G>A
,
p.Gly241Arg
?
, not provided
|
| CF databases: |
c.721G>A
,
p.Gly241Arg
(CFTR1)
?
, Identified by DGGE and direct sequencing.
|
| Predicted by SNAP2: | A: D (66%), C: D (80%), D: D (91%), E: D (91%), F: D (91%), H: D (95%), I: D (91%), K: D (95%), L: D (85%), M: D (91%), N: D (91%), P: D (95%), Q: D (91%), R: D (95%), S: D (59%), T: D (85%), V: D (91%), W: D (95%), Y: D (91%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: D, H: N, I: N, K: N, L: D, M: N, N: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: D, Y: D, |
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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.Gly241Arg 11379874:114:1461
status: NEW[hide] Role of the extracellular loop in the folding of a... Biochemistry. 2007 Jun 19;46(24):7099-106. Epub 2007 May 22. Wehbi H, Rath A, Glibowicka M, Deber CM
Role of the extracellular loop in the folding of a CFTR transmembrane helical hairpin.
Biochemistry. 2007 Jun 19;46(24):7099-106. Epub 2007 May 22., 2007-06-19 [PMID:17516627]
Abstract [show]
The folding of membrane-spanning domains into their native functional forms depends on interactions between transmembrane (TM) helices joined by covalent loops. However, the importance of these covalent linker regions in mediating the strength of helix-helix associations has not been systematically addressed. Here we examine the potential structural impact of cystic fibrosis-phenotypic mutations in the extracellular loop 2 (ECL2) on interactions between the TM3 and TM4 helices of the cystic fibrosis transmembrane conductance regulator (CFTR) in constructs containing CFTR residues 194-241. When the effects of replacements in ECL2 (including the CF-phenotypic mutants E217G and Q220R) were evaluated in a library of wild-type and mutant TM3-ECL2-TM4 hairpin constructs, we found that SDS-PAGE gel migration rates differed over a range of nearly 40% +/- the wild-type position and that decreased migration rates correlate with increasing hairpin alpha-helical content as measured by circular dichroism spectra in sodium dodecyl sulfate micelles. The decreased mobility of TM3/4 constructs by introduction of non-native residues is interpreted in terms of an elongation or "opening" of the helical hairpin and concomitant destabilization of membrane-based helix-helix interactions. Our results support a role for short loop regions in dictating the stability of membrane protein folds and highlight the interplay between membrane-embedded helix-helix interactions and loop conformation in influencing the structure of membrane proteins.
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No. Sentence Comment
145 (iii) TM3/4 mutants G241D (38) and G241R (data not shown) migrate within 2% of WT.
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ABCC7 p.Gly241Arg 17516627:145:35
status: NEW[hide] Spectrum of CFTR mutations in cystic fibrosis and ... Hum Mutat. 2000;16(2):143-56. Claustres M, Guittard C, Bozon D, Chevalier F, Verlingue C, Ferec C, Girodon E, Cazeneuve C, Bienvenu T, Lalau G, Dumur V, Feldmann D, Bieth E, Blayau M, Clavel C, Creveaux I, Malinge MC, Monnier N, Malzac P, Mittre H, Chomel JC, Bonnefont JP, Iron A, Chery M, Georges MD
Spectrum of CFTR mutations in cystic fibrosis and in congenital absence of the vas deferens in France.
Hum Mutat. 2000;16(2):143-56., [PMID:10923036]
Abstract [show]
We have collated the results of cystic fibrosis (CF) mutation analysis conducted in 19 laboratories in France. We have analyzed 7, 420 CF alleles, demonstrating a total of 310 different mutations including 24 not reported previously, accounting for 93.56% of CF genes. The most common were F508del (67.18%; range 61-80), G542X (2.86%; range 1-6.7%), N1303K (2.10%; range 0.75-4.6%), and 1717-1G>A (1.31%; range 0-2.8%). Only 11 mutations had relative frequencies >0. 4%, 140 mutations were found on a small number of CF alleles (from 29 to two), and 154 were unique. These data show a clear geographical and/or ethnic variation in the distribution of the most common CF mutations. This spectrum of CF mutations, the largest ever reported in one country, has generated 481 different genotypes. We also investigated a cohort of 800 French men with congenital bilateral absence of the vas deferens (CBAVD) and identified a total of 137 different CFTR mutations. Screening for the most common CF defects in addition to assessment for IVS8-5T allowed us to detect two mutations in 47.63% and one in 24.63% of CBAVD patients. In a subset of 327 CBAVD men who were more extensively investigated through the scanning of coding/flanking sequences, 516 of 654 (78. 90%) alleles were identified, with 15.90% and 70.95% of patients carrying one or two mutations, respectively, and only 13.15% without any detectable CFTR abnormality. The distribution of genotypes, classified according to the expected effect of their mutations on CFTR protein, clearly differed between both populations. CF patients had two severe mutations (87.77%) or one severe and one mild/variable mutation (11.33%), whereas CBAVD men had either a severe and a mild/variable (87.89%) or two mild/variable (11.57%) mutations.
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No. Sentence Comment
109 h M1K, K14X, W19X, 211delG, G27E, R31C, 237insA, 241delAT, Q39X, 244delTA, 296+2T>C, 297-3C>T, W57X+F87L, 306delTAGA, P67L, A72D, 347delC, R75Q, 359insT, 394delT, 405+4A>G, Q98R, 457TAT>G, R117H+5T, R117H+I1027T, R117L, R117P, H139R, A141D, M152V, N186K, D192N, D192del, E193X, 711+1G>A, 711+3A>G, 712-1G>T, L206F, W216X, C225R, Q237E, G241R, 852del22, 876-14del12, 905delG, 993del5, E292K, Y304X, F311del, 1161delC, R347L, R352Q, W361R, 1215delG, S364P, S434X, D443Y, S466X, C491R, T501A, I506T, F508C, I507del+F508C, F508del+L467F, 1774delCT, R553G, 1802delC, 1806delA, A559E, Y563N, 1833delT, Y569C, Y569H, Y569X, G576X, G576A, T582I, 1898+3A>G+186-13C>G, 1918delGC, R600G, L610S, G628R, 2043delG, 2118del4, E664X, 2174insA, Q689X, K698R, K716X, L732X, 2347delG, 2372del8, R764X, 2423delG, S776X, 2634insT, 2640delT, C866Y, 2752-1G>T, W882X, Y913C, V920M, 2896insAG, H939D, H939R, D979V, D985H, D993Y, 3120G>A, I1005R, 3195del6, 3293delA, 3320ins5, W1063X, A1067T, 3359delCT, T1086I, W1089X, Y1092X+S1235R, W1098X, E1104X, R1128X, 3532AC>GTA, 3548TCAT>G, M1140del, 3600G>A, R1162L, 3667ins4, 3732delA+K1200E, S1206X, 3791delC, S1235R+5T, Q1238R, Q1238X, 3849+4A>G, T1246I, 3869insG, S1255P, R1283K, F1286S, 4005+1G>T, 4006-8T>A, 4015delA, N1303H, N1303I, 4172delGC, 4218insT, 4326delTC, Q1382X, 4375-1C>T, 4382delA, D1445N, CF40kbdel4-10, Cfdel17b.
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ABCC7 p.Gly241Arg 10923036:109:336
status: NEW