ABCC7 p.Pro499Ala
| ClinVar: |
c.1495C>G
,
p.Pro499Ala
?
, not provided
|
| CF databases: |
c.1495C>G
,
p.Pro499Ala
(CFTR1)
D
, The above mutation was detected by SSCP analysis and identified by direct sequencing. It was found on the paternal chromosome in a CBAVD patient, with his maternal chromosome carrying W1282X. The mutation removes a BstNI site.
|
| Predicted by SNAP2: | A: D (59%), C: D (75%), D: D (91%), E: D (91%), F: D (91%), G: D (85%), H: D (85%), I: D (85%), K: D (91%), L: D (91%), M: D (85%), N: D (91%), Q: D (85%), R: D (91%), S: D (53%), T: D (63%), V: D (85%), W: D (91%), Y: D (91%), |
| Predicted by PROVEAN: | A: D, C: D, D: N, E: N, F: D, G: N, H: N, I: D, K: N, L: D, M: D, N: N, Q: N, R: N, S: N, T: N, V: D, W: D, Y: D, |
[switch to compact view]
Comments [show]
None has been submitted yet.
[hide] Cystic fibrosis as a cause of infertility. Reprod Biol. 2004 Jul;4(2):119-29. Jarzabek K, Zbucka M, Pepinski W, Szamatowicz J, Domitrz J, Janica J, Wolczynski S, Szamatowicz M
Cystic fibrosis as a cause of infertility.
Reprod Biol. 2004 Jul;4(2):119-29., [PMID:15297887]
Abstract [show]
Cystic fibrosis (CF) is one of the autosomal recessive diseases, caused by mutations in a gene known as cystic fibrosis transmembrane regulator (CFTR). The majority of adult males with CF (99%) is characterized by congenital bilateral absence of vas deferens (CBAVD). CBAVD is encountered in 1-2% of infertile males without CF. Females with CF are found to be less fertile than normal healthy women. In females with CF, delayed puberty and amenorrhoea are common due to malnutrition. CFTR mutations are also associated with congenital absence of the uterus and vagina (CAUV). The National Institutes of Health recommend genetic counseling for any couple seeking assisted reproductive techniques with a CF male or obstructive azoospermia which is positive for a CF mutation.
Comments [show]
None has been submitted yet.
No. Sentence Comment
62 The 5T variant produces a lower level of normal CFTR mRNA transcripts than the 7T and 9T alleles and is associated with disseminated bronchiectasis, CBAVD and epididymal obstruction [5].Arduino et al. have described a CBAVD patient with a compound heterozygosity in the CFTR gene for a stop mutation W1282X and a new missense mutation P499A.
X
ABCC7 p.Pro499Ala 15297887:62:335
status: NEW63 The P499A was found as a mild mutation, limited to the development of Wolffian duct derivatives and was revealed only in combination with a severe CFTR mutation [1].
X
ABCC7 p.Pro499Ala 15297887:63:4
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.
Comments [show]
None has been submitted yet.
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).
X
ABCC7 p.Pro499Ala 20059485:64:227
status: NEW[hide] Congenital bilateral absence of vas deferens with ... Clin Genet. 1998 Mar;53(3):202-4. Arduino C, Ferrone M, Brusco A, Garnerone S, Fontana D, Rolle L, Carbonara AO
Congenital bilateral absence of vas deferens with a new missense mutation (P499A) in the CFTR gene.
Clin Genet. 1998 Mar;53(3):202-4., [PMID:9630075]
Abstract [show]
We describe a congenital bilateral absence of the vas deferens (CBAVD) patient with a compound heterozygosity in the cystic fibrosis transmembrane regulator (CFTR) gene for a stop mutation W1282X and a new missense mutation P499A. The P499A is interpreted as a mild mutation whose phenotypic effects, in this case limited to the development of wolffian duct derivatives, are revealed only in combination with a severe CFTR mutation.
Comments [show]
None has been submitted yet.
No. Sentence Comment
2 missense the CFTR gene mutation Arduino C, Ferrone M, Brusco A, Garnerone S, Fontana D, Rolle L, Carbonara AO.Congenital bilateral absence of vas deferens with a new missense mutation (P499A)in the CFTR gene.
X
ABCC7 p.Pro499Ala 9630075:2:185
status: NEW4 0 Munksgaard, 1998 We describe a congenital bilateral absence of the vas deferens (CBAVD) patient with a compound heterozygosity in the cystic fibrosis transmembrane regulator ( C n R ) gene for a stop mutation W1282X and a new missense mutation P499A.The P499A is interpreted as a mild mutation whose phenotypic effects, in this case limited to the development of wolffian duct derivatives,are revealed only in combination with a severe CFTR mutation.
X
ABCC7 p.Pro499Ala 9630075:4:246
status: NEWX
ABCC7 p.Pro499Ala 9630075:4:256
status: NEW11 The present study reports a CBAVD patient with a compound heterozygosity in the CFTR gene for a stop mutation (W1282X) and a new missense mutation (P499A).
X
ABCC7 p.Pro499Ala 9630075:11:148
status: NEW12 The effects of this genotype are 202 (P499A) in C Arduino., M Ferroneb, A Bruscob,S Gameroneb, D Fontaria', L Rolledand A 0 Carbonarab a servizioUniversitario Convenzionato di Genetica Medica.
X
ABCC7 p.Pro499Ala 9630075:12:38
status: NEW31 P499A and W1289X mutations are also included.
X
ABCC7 p.Pro499Ala 9630075:31:0
status: NEW34 The wild type allele produced three fragments of 257, 223 and 11 bp; the P499A mutations yielded two fragments of 257 and 234 bp.
X
ABCC7 p.Pro499Ala 9630075:34:73
status: NEW39 Results Patient SA analysed for the 12 CF mutations proved positive for W128X, which was inherited from the mother (1-2), Direct sequencing of exon 10, which displayed a band shift, showed C-.G transversion at position 1627 that changed residue 499 from Pro to Ala (P499A).
X
ABCC7 p.Pro499Ala 9630075:39:245
status: NEWX
ABCC7 p.Pro499Ala 9630075:39:266
status: NEW41 The P499A was inherited from the father (1-1) and it is also present in the sister (11-3).
X
ABCC7 p.Pro499Ala 9630075:41:4
status: NEW42 The P499A behaves as allelic to W1282X.
X
ABCC7 p.Pro499Ala 9630075:42:4
status: NEW44 Fig. la displays the haplotypes deduced from the segregation of six CFTR-linked Arduino et al. polymorphic sites; note that the 5T variant and P499A are in trans in 1-1.
X
ABCC7 p.Pro499Ala 9630075:44:145
status: NEW45 Screening of 200 normal chromosomes from healthy individuals detected the new P499A mutation in two subjects YO).
X
ABCC7 p.Pro499Ala 9630075:45:78
status: NEW46 None of the 105 CF uncharacterised chromosomes carried the P499A.
X
ABCC7 p.Pro499Ala 9630075:46:59
status: NEW49 The CFTR genotype of our patient is represented by a severe mutation (W1282X) and by a new missense substitution P499A.
X
ABCC7 p.Pro499Ala 9630075:49:113
status: NEW50 Several considerations suggest that P499A is not a neutral polymorphic variant but a mild mutation that in the context of a peculiar CFTR genotype can be associated with CBAVD.
X
ABCC7 p.Pro499Ala 9630075:50:36
status: NEW53 In comparison with these mutants, P499A appears even milder; indeed the patient`s healthy father carries P499A in one chromosome and the 5T allele in the other without showing any sign of CFTR dysfunction.
X
ABCC7 p.Pro499Ala 9630075:53:34
status: NEWX
ABCC7 p.Pro499Ala 9630075:53:105
status: NEW54 This interpretation is also substantiated by the absence of P499A on 306 CF chromosomes.
X
ABCC7 p.Pro499Ala 9630075:54:60
status: NEW55 In conclusion, P499A appears to belong to the category of substitutions that slightly affect the CFTR function and can therefore give rise to a mild phenotype such as CBAVD only in combination with a severe mutation.
X
ABCC7 p.Pro499Ala 9630075:55:15
status: NEW