ABCC7 p.Leu137Arg
| ClinVar: |
c.410T>G
,
p.Leu137Arg
?
, not provided
c.410T>A , p.Leu137His ? , not provided |
| CF databases: |
c.410T>A
,
p.Leu137His
(CFTR1)
D
, The above mutation was detected by SSCP/heteroduplex analysis and characterised by direct sequencing. It was not previously observed in over 100 non-[delta]F508 CF chromosomes. L137H was observed in an adult male presenting only with male infertility due to CBAVD. This sample was referred from the Leeds DNA lab by Lucy Ellis. His other mutation is [delta]F508.
c.410T>G , p.Leu137Arg (CFTR1) ? , This French CF patient has [delta]F508 on the other CF chromosome. This substitution creates a Cfo I site. |
| Predicted by SNAP2: | A: D (63%), C: D (53%), D: D (91%), E: D (85%), F: N (57%), G: D (91%), H: D (85%), I: D (59%), K: D (91%), M: N (66%), N: D (85%), P: D (91%), Q: D (80%), R: D (91%), S: D (80%), T: D (80%), V: N (61%), W: D (85%), Y: D (80%), |
| Predicted by PROVEAN: | A: N, C: N, D: D, E: D, F: N, G: D, H: D, I: N, K: D, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: N, W: D, Y: N, |
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[hide] CFTR mutation combinations producing frequent comp... Hum Mutat. 2012 Nov;33(11):1557-65. doi: 10.1002/humu.22129. Epub 2012 Jul 2. El-Seedy A, Girodon E, Norez C, Pajaud J, Pasquet MC, de Becdelievre A, Bienvenu T, des Georges M, Cabet F, Lalau G, Bieth E, Blayau M, Becq F, Kitzis A, Fanen P, Ladeveze V
CFTR mutation combinations producing frequent complex alleles with different clinical and functional outcomes.
Hum Mutat. 2012 Nov;33(11):1557-65. doi: 10.1002/humu.22129. Epub 2012 Jul 2., [PMID:22678879]
Abstract [show]
Genotype-phenotype correlations in cystic fibrosis (CF) may be difficult to establish because of phenotype variability, which is associated with certain CF transmembrane conductance regulator (CFTR) gene mutations and the existence of complex alleles. To elucidate the clinical significance of complex alleles involving p.Gly149Arg, p.Asp443Tyr, p.Gly576Ala, and p.Arg668Cys, we performed a collaborative genotype-phenotype correlation study, collected epidemiological data, and investigated structure-function relationships for single and natural complex mutants, p.[Gly576Ala;Arg668Cys], p.[Gly149Arg;Gly576Ala;Arg668Cys], and p.[Asp443Tyr;Gly576Ala;Arg668Cys]. Among 153 patients carrying at least one of these mutations, only three had classical CF and all carried p.Gly149Arg in the triple mutant. Sixty-four had isolated infertility and seven were healthy individuals with a severe mutation in trans, but none had p.Gly149Arg. Functional studies performed on all single and natural complex mutants showed that (1) p.Gly149Arg results in a severe misprocessing defect; (2) p.Asp443Tyr moderately alters CFTR maturation; and (3) p.Gly576Ala, a known splicing mutant, and p.Arg668Cys mildly alter CFTR chloride conductance. Overall, the results consistently show the contribution of p.Gly149Arg to the CF phenotype, and suggest that p.[Arg668Cys], p.[Gly576Ala;Arg668Cys], and p.[Asp443Tyr;Gly576Ala;Arg668Cys] are associated with CFTR-related disorders. The present study emphasizes the importance of comprehensive genotype-phenotype and functional studies in elucidating the impact of mutations on clinical phenotype. Hum Mutat 33:1557-1565, 2012. (c) 2012 Wiley Periodicals, Inc.
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No. Sentence Comment
107 of patients Main diagnosis Additional information Age at diagnosis Sweat test (Cl-,mmol/L) Allele 1 Allele 2 1 FBA Fetal death 20 wg NA p.[Gly576Ala;Arg668Cys] p.Ser1235Arg 1 FBA Unknown outcome p.Arg668Cys p.Phe508del 1 FBA Not CF at birth 38 wg NA p.[Asp443Tyr;Gly576Ala;Arg668Cys] NI 1 FBA Not CF at birth 28 wg NA p.[Gly576Ala;Arg668Cys] NI 1 Healthy CF patient`s mother NA NA p.[Asp443Tyr;Gly576Ala;Arg668Cys] p.Phe508del 1 Healthy Newborn, elevated IRT but normal ST (not CF) Birth <30 p.[Gly576Ala;Arg668Cys] p.Phe508del 1 Healthy Mother of a CF fetus (p.[Phe508del]+ [phe508del]) NA NA p.[Gly576Ala;Arg668Cys] p.Phe508del 1 Healthy Mother of a fetus with FBA but not affected with CF NA NA p.[Gly576Ala;Arg668Cys] p.Phe508del 2 Healthy Mother of a fetus with FBA but not affected with CF NA NA p.[Gly576Ala;Arg668Cys] NI 1 Healthy CF patient`s mother 59 y NA p.[Gly576Ala;Arg668Cys] p.Phe508del 1 Healthy CF patient`s mother NA NA p.[Gly576Ala;Arg668Cys] p.[Ser912Leu;Asn1303Lys] 1 Healthy CF patient`s mother 32 y NA p.[Gly576Ala;Arg668Cys] p.Leu137Arg 1 Healthy CF carrier`s partner NA NA p.[Gly576Ala;Arg668Cys] c.
X
ABCC7 p.Leu137Arg 22678879:107:1052
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
108 g D44G, 300delA, W57X, 405+1G>A, D110H, E116K, 541del4, 542del7, L137R, 621+2T>G, I175V, H199R, H199Y, C225X, V232D, Q290X, E292X, G314V, T338I, 1221delCT, W401X, Q452P, I502T, 1716+2T>C, G544S, R560S, A561E, V562I, Y569D, 1898+3A>G, 1898+5G>A, G628R(G>A), 2143delT, G673X, R851X, Q890X, S977F, 3129del4, 3154delG, 3271+1G>A, G1061R, R1066L, R1070W, 3601-17T>C, S1196X, 3732delA, G1249R, 3898insC, 4374+1G>A, del25kb.
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ABCC7 p.Leu137Arg 10923036:108:65
status: NEW