ABCMdb

ABCC7 p.Ile506Ser

ClinVar:	c.1518C>G , p.Ile506Met ? , not provided c.1517T>C , p.Ile506Thr ? , not provided c.1516A>C , p.Ile506Leu ? , not provided c.1516A>G , p.Ile506Val N , Benign c.1517T>G , p.Ile506Ser ? , not provided
CF databases:	c.1516A>C , p.Ile506Leu (CFTR1) D , The mutation was found in one Swedish CF patient by multiplex heteroduplex analysis on an MDE gel. The patient carried [delta]F508 on the other allele; the patient had sweat chloride of 103 meq/l, pancreatic sufficient, and mild lung disease. c.1517T>C , p.Ile506Thr (CFTR1) ? , The whole coding and flanking sequence has been screened by DGGE, and no other alteration could be found except known polymorphisms. This second mutation at codon 506 ( the first, 1506S, was described by Deufel) was thoroughly checked by two different sequences from different PCR products. c.1517T>G , p.Ile506Ser (CFTR1) ? , Allele specific amplification and PAA electrophoresis of exon 10 fragments had given discrepant results. By direct sequencing, we found a T to G transversion at nucleotide position 1649, exchanging a isoleucine for a serine (I506S). The second mutation is [delta]F508. The heteroduplex I506S/[delta]F508 can be distinguished from wt/[delta]F508 duplices, allowing for rapid screening of the mutation.
Predicted by SNAP2:	A: D (95%), C: D (95%), D: D (95%), E: D (95%), F: D (95%), G: D (95%), H: D (95%), K: D (95%), L: D (85%), M: D (66%), N: D (95%), P: D (95%), Q: D (95%), R: D (95%), S: D (95%), T: D (95%), V: N (87%), W: D (95%), Y: D (95%),
Predicted by PROVEAN:	A: D, C: D, D: D, E: D, F: D, G: D, H: D, K: D, L: N, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: N, W: D, Y: D,

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Publications
[hide] Detecting CFTR gene mutations by using primer olig... Clin Chem. 1997 Jul;43(7):1151-8. Braun A, Little DP, Koster H
Detecting CFTR gene mutations by using primer oligo base extension and mass spectrometry.
Clin Chem. 1997 Jul;43(7):1151-8., [PMID:9216450]

Abstract [show]
A new method for the reliable identification of localized variations in DNA by detection of associated diagnostic products with matrix-assisted laser desorption ionization time-of-flight mass spectrometry is described. The diagnostic products are generated by the primer oligo base extension (PROBE) reaction, which requires a single detection primer complementary to a region down-stream of a target strand's variable site. On addition of a polymerase, three dNTPs, and the fourth nucleotide in dideoxy form, the primer is extended through the mutation region until the first ddNTP is incorporated; the mass of the extension products determines the composition of the variable site. Tests for five cystic fibrosis mutations, including two exon 11 sites measured in a biplex reaction, and for differentiating between three common alleles of the poly(T) tract at the intron 8 splice acceptor site of the CFTR gene are presented. All experimental steps required for PROBE are amenable to the high degree of automation desirable for a high-through-put diagnostic setting. Furthermore, it requires no fluorescent, chemiluminescent, or radioactive labeling; the mass signals measured offer a far more analytically definitive signal, leading in all cases to high-quality unambiguous and easily interpreted results.

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No. Sentence Comment
68 In the ddT and ddC reactions, the 7288.8-Da 24-mer primer is converted entirely to products consistent with the addition of 5 (8842.8 Da, Fig. 2a) and 14 (11 609.7 Da, Fig. 2b) bases, respectively; the result in Fig. 2a is consistent with not only wild-type, but also a genotype homo- or heterozygous for I506S and ⌬I507. Login to comment
69 To resolve this ambiguity, these are readily distinguished on consideration of the ddC reaction, in which wild-type, I506S, and ⌬I507 alleles yield products of dramatically different mass (11 609 vs 9468 and 10 653 Da, respectively). Login to comment
73 Further genotype assignment for patients homozygous for ⌬F508 (Fig. 2, e and f), compound heterozygote ⌬I507/⌬F508 (Fig. 2, g and h), and heterozygote for I506S (Fig. 2, i and k) are equally definitive, even though the two molecular species of the peak in Fig. 2h (⌬m ϭ 9 Da) are not resolved. Login to comment
96 a and b, homozygous wild-type; c and d, heterozygote wild-type/⌬F508; e and f, homozygous ⌬F508; g and h, compound heterozygote ⌬I507/⌬F508; i and k, heterozygote wild-type/I506S. Login to comment