ABCC7 p.Leu183Ile
| ClinVar: |
c.547C>A
,
p.Leu183Ile
?
, not provided
|
| CF databases: |
c.547C>A
,
p.Leu183Ile
(CFTR1)
D
, This mutation was found in a CBAVD Pakistani male, who also has the 5T allele (phase unknown).
|
| Predicted by SNAP2: | A: D (85%), C: D (80%), D: D (95%), E: D (95%), F: D (85%), G: D (95%), H: D (91%), I: D (59%), K: D (95%), M: D (75%), N: D (95%), P: D (95%), Q: D (91%), R: D (80%), S: D (91%), T: D (91%), V: D (63%), W: D (91%), Y: D (91%), |
| Predicted by PROVEAN: | A: D, C: D, 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] 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
11 Other known CFTR mutations identified were V456A, G542X, R668C, I1027T, D1152, R1162L, W1282X, and L183I.
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ABCC7 p.Leu183Ile 17035430:11:99
status: NEW87 A fourth mutation (L183I) was found that was thought to be novel, but in the course of manuscript preparation and review this mutation was found to have been previously reported.
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ABCC7 p.Leu183Ile 17035430:87:19
status: NEW113 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.Leu183Ile 17035430:113:335
status: NEW124 The most phenotypically severe CFTR mutation, ⌬F508, was present in 12% of subjects in this study, compared to the general frequency of 3% in the white population in the United States.39,40 The R75Q mutation frequency was 14% in this study, compared to the general frequency of 1% in Northern Europeans.41 The intron 8 5T polymorphism was present in 17% of subjects in this study, compared to 5 to 10% in the general population.42,43 CFTR mutations identified in this study, including ⌬F508, R75Q, R117H, S1235R, D1152, L183I, and IVS8 5T, have been associated with mild symptoms of CF41,44-46 or with atypical manifestations of CF, such as isolated bronchiectasis14-17,19,20,22,23,25-27 and CBAVD.42,43,47 This study also reports three novel CFTR mutations, each in a separate patient with normal sweat chloride level: A394V, C1344S, and F650L.
X
ABCC7 p.Leu183Ile 17035430:124:534
status: NEW[hide] Do common in silico tools predict the clinical con... Clin Genet. 2010 May;77(5):464-73. Epub 2009 Jan 6. Dorfman R, Nalpathamkalam T, Taylor C, Gonska T, Keenan K, Yuan XW, Corey M, Tsui LC, Zielenski J, Durie P
Do common in silico tools predict the clinical consequences of amino-acid substitutions in the CFTR gene?
Clin Genet. 2010 May;77(5):464-73. Epub 2009 Jan 6., [PMID:20059485]
Abstract [show]
Computational methods are used to predict the molecular consequences of amino-acid substitutions on the basis of evolutionary conservation or protein structure, but their utility in clinical diagnosis or prediction of disease outcome has not been well validated. We evaluated three popular computer programs, namely, PANTHER, SIFT and PolyPhen, by comparing the predicted clinical outcomes for a group of known CFTR missense mutations against the diagnosis of cystic fibrosis (CF) and clinical manifestations in cohorts of subjects with CF-disease and CFTR-related disorders carrying these mutations. Owing to poor specificity, none of tools reliably distinguished between individual mutations that confer CF disease from mutations found in subjects with a CFTR-related disorder or no disease. Prediction scores for CFTR mutations derived from PANTHER showed a significant overall statistical correlation with the spectrum of disease severity associated with mutations in the CFTR gene. In contrast, PolyPhen- and SIFT-derived scores only showed significant differences between CF-causing and non-CF variants. Current computational methods are not recommended for establishing or excluding a CF diagnosis, notably as a newborn screening strategy or in patients with equivocal test results.
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No. Sentence Comment
64 Mutations in the CFTR gene grouped by clinical category Cystic fibrosis CFTR-related disease No disease T338I D614G L320V V920L L90S M470V H199R S1251N I203M G550R P111A I148T Q1291H R560K L1388Q L183I R170H I1027T S549R D443Y P499A L1414S T908N R668C S549N A455E E1401K Q151K G27E I1234L Y563N R347P C866R S1118C P1290S R75Q A559T V520F P841R M469V E1401G P67L G85E S50Y E1409K R933G G458V G178R Y1032C R248T I980K G85V V392G L973P L137H T351S R334W I444S V938G R792G R560T R555G L1339F D1305E P574H V1240G T1053I D58G G551D L1335P I918M F994C S945L L558S F1337V R810G D1152H G1247R P574S R766M D579G W1098R H949R F200I R352Q L1077P K1351E M244K L206W M1101K D1154G L375F N1303K R1066C E528D D110Y R347H R1070Q A800G P1021S S549K A1364V V392A damaging` (is supposed to affect protein function or structure) and 'probably damaging` (high confidence of affecting protein function or structure).
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ABCC7 p.Leu183Ile 20059485:64:196
status: NEW[hide] Characterisation of mutations and genotype-phenoty... J Cyst Fibros. 2008 Mar;7(2):110-5. Epub 2007 Aug 22. Shastri SS, Kabra M, Kabra SK, Pandey RM, Menon PS
Characterisation of mutations and genotype-phenotype correlation in cystic fibrosis: experience from India.
J Cyst Fibros. 2008 Mar;7(2):110-5. Epub 2007 Aug 22., [PMID:17716958]
Abstract [show]
BACKGROUND: Very little is known about the genetics of cystic fibrosis (CF) from the Indian subcontinent. The aims of the study were to identify the mutations and study the relation of genotype with phenotype in Indian children with CF. METHODS: A total of 100 patients with CF were screened for mutations in the CFTR gene. These included c.1521_1523delCTT (p.F508del) and c.3849+10 kb C>T mutations followed by single strand conformation polymorphism/heteroduplex analysis for mutations in 19 out of 27 exons of the CFTR gene. RESULTS: At least one mutation was identified in 40 patients. The most common mutation identified was p.F508del; 20 patients were homozygous and 13 heterozygous. In addition, c.3849+10 kb C>T, c.1161delC, and p.S549N were identified in two patients each and p.R352Q, p.R1158X and p.R75Q were identified in one patient each. Three novel mutations, viz. c.1002-7_1002-5delTTT, p.G149X and p.L183I were also identified. Majority of patients who were p.F508del positive originated from Pakistan and north-western states of India. The phenotypes of all patients were classical. Genotype-phenotype correlation revealed that p.F508del positive patients had a more severe disease, manifesting at an earlier age. CONCLUSIONS: A strategy for mutation screening for CF in India must involve testing for p.F508del followed by c.1161delC, c.3849+10 kb C>T and p.S549N. There is a need for large multicentric studies using more sensitive techniques for the identification of mutations in Indian CF patients.
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No. Sentence Comment
7 Three novel mutations, viz. c.1002-7_1002-5delTTT, p.G149X and p. L183I were also identified.
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ABCC7 p.Leu183Ile 17716958:7:66
status: NEW83 A mutation (p.L183I) was detected in exon 5.
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ABCC7 p.Leu183Ile 17716958:83:14
status: NEW85 Novel mutations identified Three mutations (c.1002-7_1002-5delTTT, p.L183I, p. G149X) unpublished so far (Table 2) were detected in one patient each.
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ABCC7 p.Leu183Ile 17716958:85:69
status: NEW86 While c.1002-7 to 1002-5delTTT was detected in homozygous state, p.L183I and p.G149X were detected in heterozygous state.
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ABCC7 p.Leu183Ile 17716958:86:67
status: NEW94 Severe clinical phenotype was seen in a patient with p.G149X mutation and low CF score, whereas milder CF phenotype was seen in the two patients with c.1002-7_1002- 5delTTT and p.L183I.
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ABCC7 p.Leu183Ile 17716958:94:179
status: NEW116 The frequency Table 2 New mutations identified in patients with cystic fibrosis Mutation 1 Mutation 2 Mutation 3 Exon/intron Exon 4 Intron 6b Exon 5 Mutation p.G149X (c.577GNT) c.1002-7_1002-5delTTT p.L183I (c.679CNA) Resulting change Stop codon at 149 Deletion of 3 bp in intron 6b/exon7 boundary Leucine to isoleucine at 183 Genotype of the patient p.[F508del]+[G149X] c.
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ABCC7 p.Leu183Ile 17716958:116:201
status: NEWX
ABCC7 p.Leu183Ile 17716958:116:298
status: NEW117 [1002-7_1002-5delTTT]+[1002-7_1002-5delTTT] p.[L183I]+[?]
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ABCC7 p.Leu183Ile 17716958:117:47
status: NEW125 2 p.[L183I]+[?]
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ABCC7 p.Leu183Ile 17716958:125:5
status: NEW149 p.L183I is a substitution of cytosine by adenosine at the nucleotide position 679, which changes the amino acid 183 to isoleucine from leucine.
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ABCC7 p.Leu183Ile 17716958:149:2
status: NEW