ABCC7 p.Glu1409Lys
| ClinVar: |
c.4225G>A
,
p.Glu1409Lys
?
, not provided
|
| CF databases: |
c.4225G>A
,
p.Glu1409Lys
(CFTR1)
D
, This mutation was detected by DGGE method from a Spanish CBAVD patient carriying the N1303K mutation in the other allele.It was not found in 200 CF chromosomes. It destroys a BsmI restriction site.
c.4226A>T , p.Glu1409Val (CFTR1) ? , This mutation was detected by DGGE in exon 23 from a patient from southern France. The substitution was not found in 150 normal chromosomes. It destroys a BsmI restriction site. |
| Predicted by SNAP2: | A: N (61%), C: N (61%), D: N (97%), F: N (53%), G: D (59%), H: N (61%), I: D (59%), K: D (53%), L: D (53%), M: N (72%), N: N (87%), P: D (71%), Q: N (66%), R: D (59%), S: N (61%), T: N (57%), V: N (53%), W: N (53%), Y: N (53%), |
| Predicted by PROVEAN: | A: D, C: D, D: N, F: D, G: D, H: D, I: D, K: N, L: D, M: D, N: N, P: D, Q: N, R: D, S: N, T: D, V: D, W: D, Y: D, |
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[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.Glu1409Lys 20059485:64:372
status: NEW[hide] Multiplex ligation-dependent probe amplification i... J Mol Diagn. 2008 Jul;10(4):368-75. Epub 2008 Jun 13. Schrijver I, Rappahahn K, Pique L, Kharrazi M, Wong LJ
Multiplex ligation-dependent probe amplification identification of whole exon and single nucleotide deletions in the CFTR gene of Hispanic individuals with cystic fibrosis.
J Mol Diagn. 2008 Jul;10(4):368-75. Epub 2008 Jun 13., [PMID:18556774]
Abstract [show]
A disparity between Caucasian and Hispanic mutation detection for cystic fibrosis continues to exist, although the carrier frequency is only moderately lower in Hispanics. We aimed to identify exonic rearrangements that remained undetected by conventional methods. In seven of 32 cystic fibrosis-affected self-identified Hispanics for whom only one or no mutations were identified by extensive molecular testing, exon deletions appeared to be present with a multiplex ligation-dependent probe amplification (MLPA) assay. Two recurrent deletions (of exons 2-3 and exons 22-23) were identified in one and three patients, respectively (12.5%, 11.1% of unidentified alleles). Two apparently novel deletions (exons 6b and 20) were identified in three additional patients. Subsequent sequencing to characterize deletion breakpoints, however, identified single nucleotide deletions at the probe binding sites close to the ligation point. All resulted in false positive MLPA deletion signals. Interestingly, these mutations were not common in Caucasians, and one (935delA) was common in U.S. Hispanics. On examination of all probe binding sites, we identified a total of 76 reported mutations and five silent variants that immediately surrounded the MLPA ligation sites, with 22 occurring in non-Caucasians. These mutations are not all rare. Thus, apparent exon deletions by MLPA may indicate the presence of both large deletions and point mutations, with important implications for pan-ethnic MLPA testing in cystic fibrosis and other genetic conditions.
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No. Sentence Comment
112 Mutations under MLPA Ligation Sites Exon Probe length (nt) Ligation site sequence Mutations in area of ligation site sequence* 1,5Ј UTR 154 5Ј-GAGCAAAT-TTGGGGCC-3Ј N/A 1,5Ј UTR 238 5Ј-AAAGGGTT-GAGCGGCA-3Ј 2 198 5Ј-TTGGTATA-TGTCTGAC-3Ј (5) 3 136 5Ј-CTGCTAGT-GTTGCCAA-3Ј (3) 3 220 5Ј-TTCAAAGA-AAAATCCT-3Ј 4 247 5Ј-AGAATCAT-AGCTTCCT-3Ј 444delA, African; 451del8, Chinese; (6) 5 346 5Ј-AAATAAGT-ATTGGACA-3Ј Q179K, Hispanic (7) 6a 274 5Ј-GAGTTGTT-ACAGGCGT-3Ј L218X, Pakistani (4) 6b 301 5Ј-ATTTTCAA-TCATTTCT-3Ј 935delA, Hispanic; 936delTA, Hispanic (3) 7 337 5Ј-ACTTCAAT-AGCTCAGC-3Ј S307N, Turkish (9) 8, IVS 8 364 5Ј-TTTCTAGA-TTAAGAAG-3Ј N/A 9, IVS 8 391 5Ј-TCCATCAC-ACTGGTAG-3Ј N/A 10 463 5Ј-TCCACTGT-GCTTAATT-3Ј H484Y, Hispanic; S485C, Chinese-Caucasian (5) 11 418 5Ј-CAGAGAAA-GACAATAT-3Ј K536X, Iranian; 1742delAC, Japanese (5) 12, IVS 12 292 5Ј-TGCATTTT-ACCTCTTG-3Ј N/A 13 142 5Ј-CAGATTCT-GAGCAGGG-3Ј (1) 14a 160 5Ј-GTATGTGT-TCCATGTA-3Ј (3) 14b 178 5Ј-CTGCTTCT-TTGGTTGT-3Ј 2766del8, Tunisian (1) 15 204 5Ј-GCTTGCTA-TGGGATTC-3Ј (1) 16, IVS 16 229 5Ј-GATGTAAT-AGCTGTCT-3Ј N/A 17a 256 5Ј-TGCAACAA-AGATGTAG-3Ј 3171delC, Hispanic; 3173delAC, Turkish; F1016S, Hispanic (5) 17b 283 5Ј-CAGTATGT-AAATTCAG-3Ј H1085R, Japanese (4) 18 310 5Ј-CCATGAAT-ATCATGAG-3Ј M1137R, Hispanic (6) 19 353 5Ј-TCTGTGTA-TTTTGCTG-3Ј 3791delC, African-American (2) 20 382 5Ј-CTTGGGAT-TCAATAAC-3Ј 3960delA, Hispanic (2) 21 409 5Ј-TGCAACTT-TCCATATT-3Ј W1316X, African-American (2) 22 436 5Ј-GAACAGTT-TCCTGGGA-3Ј No mutations 23 148 5Ј-CCAGCATT-GCTTCTAT-3Ј M1407T, Turkish; E1409K, Hispanic (2) 24 190 5Ј-ATCCAGAA-ACTGCTGA-3Ј No mutations 24 172 5Ј-CTCCTCTT-TCAGAGCA-3Ј UTR, untranslated region; IVS, intervening sequence; N/A, not applicable, probes not in coding region; No mutations, no reported mutations are present in the area of the ligation site sequence, regardless of ethnicity.
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ABCC7 p.Glu1409Lys 18556774:112:1888
status: NEW