ABCMdb

ABCC7 p.Lys464Asn

ClinVar:	c.1392G>T , p.Lys464Asn ? , not provided
Predicted by SNAP2:	A: D (95%), C: D (95%), D: D (95%), E: D (95%), F: D (95%), G: D (95%), H: D (95%), I: D (95%), L: D (95%), M: D (95%), N: D (91%), P: D (95%), Q: D (95%), R: D (95%), S: D (95%), T: D (95%), V: D (95%), W: D (95%), Y: D (95%),
Predicted by PROVEAN:	A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D,

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Publications
[hide] Influence of the duplication of CFTR exon 9 and it... J Mol Diagn. 2009 Sep;11(5):488-93. El-Seedy A, Dudognon T, Bilan F, Pasquet MC, Reboul MP, Iron A, Kitzis A, Ladeveze V
Influence of the duplication of CFTR exon 9 and its flanking sequences on diagnosis of cystic fibrosis mutations.
J Mol Diagn. 2009 Sep;11(5):488-93., [PMID:19710401]

Abstract [show]
The DNA sequences of seven regions in the human genome were examined for sequence identity with exon 9 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which is mutated in cystic fibrosis, and its intronic boundaries. These sequences were 95% to 96% homologous. Based on this nucleotide sequence similarity, PCR primers for CFTR exon 9 can potentially anneal with other homologous sequences in the human genome. Sequence alignment analysis of the CFTR exon 9 homologous sequences revealed that five registered mutations in the Cystic Fibrosis Mutation Database may be due to the undesired annealing of primers to a homologous sequence, resulting in inappropriate PCR amplification. For this reason, we propose that certain pseudomutations may result from the similarity between CFTR exon 9 (and its flanking introns) and related sequences in the human genome. Here we show that two mutations previously described in the CFTR database (c.1392 + 6insC; c.1392 + 12G>A) were inappropriately attributed to two individuals who sought carrier testing. A more detailed study by either direct sequencing or subcloning and sequencing of PCR products using specially designed primers revealed that these apparent mutations were not, in fact, present in CFTR. In addition, we present new PCR conditions that permit specific amplification of CFTR exon 9 and its flanking regions.

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Sentences [show]
No. Sentence Comment
99 Several variations have been identified in exon 9, including four possible mutations shown in Figure 2A: p.Lys464Asn, c.1328_1329delAT, c.1235delC, and p.Asn416ser (http://www.genet.sickkids.on.ca/cftr/; last accessed 24/12/2008) [Personal communications: p.Lys464Asn (E. Bleth, V. Gaston, P. Gautry), c.1328_1329delAT (T. Bienvenu, L. Tchertkoff, C. Cazeneuve, C Beldjord), c.1235delC (C. Fe´rec), and p.Asn416Ser (L. Picci, M. Cameran, O. Marangon, D. Marzenta, M. Scarpa)]. Login to comment
133 Mutations in CFTR Exon 9 and its Intronic Boundaries that Have Homologous Sequences in Other Chromosomes CFTR mutation Common nomenclature Nucleotide change Site of mutation* Consequences p.Lys464Asn K464N G to T at 1392 Exon 9 (no. 10) Lys to Asn at 464; mRNA splicing defect? Login to comment
145 These include p.Lys464Asn, c.1328_1329delAT, c.1235delC, and p.Asn416Ser in exon 9, and c.1392 ϩ 6insC; c.1392 ϩ 12GϾA in intron 9. Login to comment

[hide] Consequences of partial duplications of the human ... J Cyst Fibros. 2013 Jul;12(4):407-10. doi: 10.1016/j.jcf.2012.11.006. Epub 2012 Dec 21. El-Seedy A, Pasquet MC, Bienvenu T, Bieth E, Audrezet MP, Kitzis A, Ladeveze V
Consequences of partial duplications of the human CFTR gene on cf diagnosis: mutations or ectopic variations.
J Cyst Fibros. 2013 Jul;12(4):407-10. doi: 10.1016/j.jcf.2012.11.006. Epub 2012 Dec 21., [PMID:23261175]

Abstract [show]
CFTR exon 10 and its flanking regions are duplicated in the human genome. These duplications present mutations compared to the normal exon 10 sequence. Due to the polymorphic sequence of the 3' intron 9 sequence, it may appear difficult to sequence exon 10 and some mutations described in this exon could, in fact, be variations observed in an ectopic duplicated sequence. In our previous work we described a methodology to carry out PCR only of exon 10 and not of ectopic regions. In this work, we analyzed mutations described in the CF data base as being CFTR mutations but also found in ectopic regions: c.1392G>T, c.1338_1339delAT, c.1235delC, and c.1247A>G. We have shown that these mutations appear to be authentic mutations in CFTR exon 10 and not ectopic variations in analyzed patients. These mutations validate the usefulness of our new strategy in the mutation analysis of this region of CFTR.

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Sentences [show]
No. Sentence Comment
23 Indeed, our previous results suggested that several mutations described in exon 10 and its flanking regions may in fact be ectopic variations from sequences detected in pseudogenes: c.1392GNT (p.Lys464Asn, 1524GNT), c.1338_13 39delAT (p.Ile444X, 1460delAT), c.1235delC (p.Ala412GlufsX 30, 1367delC), and c.1247ANG (p.Asn416Ser, N416S) [4]. Login to comment
77 The c.1392GNT mutation is a transversion in exon 10, which causes a change of Lysine to Asparagine at position 464 of the CFTR polypeptide. Login to comment
79 The effect of the predicted splicing mutation c.1392GNT (p.Lys464Asn, K464N) was analyzed by computer-assisted splice-site prediction using Human Splicing folder website. Login to comment