ABCMdb

ABCC7 p.Ser1235Asn

ClinVar:	c.3705T>G , p.Ser1235Arg N , Benign/Likely benign
CF databases:	c.3705T>G , p.Ser1235Arg N , Non CF-causing ; CFTR1: The S1235R mutation (T->G at nucleotide position 3837) in exon 19 was found in 2 out of 34 unrelated Belgian CF chromosomes (7 [delta]F508 and 27 non-[delta] CF chromosomes.
Predicted by SNAP2:	A: N (61%), C: D (75%), D: D (59%), E: N (57%), F: D (85%), G: D (59%), H: D (53%), I: D (71%), K: N (57%), L: D (59%), M: D (71%), N: N (61%), P: D (63%), Q: N (57%), R: D (75%), T: N (72%), V: D (66%), W: D (91%), Y: D (66%),
Predicted by PROVEAN:	A: N, C: D, D: N, E: N, F: D, G: N, H: N, I: D, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, T: N, V: N, W: D, Y: N,

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Publications
[hide] Comparative ex vivo, in vitro and in silico analys... J Cyst Fibros. 2015 Feb 27. pii: S1569-1993(15)00039-9. doi: 10.1016/j.jcf.2015.02.002. Ramalho AS, Clarke LA, Sousa M, Felicio V, Barreto C, Lopes C, Amaral MD
Comparative ex vivo, in vitro and in silico analyses of a CFTR splicing mutation: Importance of functional studies to establish disease liability of mutations.
J Cyst Fibros. 2015 Feb 27. pii: S1569-1993(15)00039-9. doi: 10.1016/j.jcf.2015.02.002., [PMID:25735457]

Abstract [show]
The Cystic Fibrosis p.Ile1234Val missense mutation actually creates a new dual splicing site possibly used either as a new acceptor or donor. Here, we aimed to test the accuracy of in silico predictions by comparing them with in vitro and ex vivo functional analyses of this mutation for an accurate CF diagnosis/prognosis. To this end, we applied a new in vitro strategy using a CFTR mini-gene which includes the complete CFTR coding sequence plus intron 22 (short version) which allows the assessment of alternatively spliced mRNA levels as well as the properties of the resulting abnormal CFTR protein regarding processing, intracellular localization and function. Our data demonstrate that p.Ile1234Val leads to usage of the alternative splicing donor (but not acceptor) resulting in alternative CFTR transcripts lacking 18nts of exon 22 which produce a truncated CFTR protein with residual Cl- channel function. These results recapitulate data from native tissues of a CF patient. In conclusion, the existing in silico prediction models have limited application and ex vivo functional assessment of mutation effects should be made. Alternatively the in vitro strategy adopted here can be applied to assess the disease liability of mutations for an accurate CF diagnosis/prognosis.

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No. Sentence Comment
225 The CFTR protein resulting from the "fish revertant" (c.3704G N A) which reverts the splicing of IVS22, is also correctly processed (Fig. 4B, lane 3), despite the fact that it has two missense mutations (p.Ile1234Val-c.3700A N G and p.Ser1235Asn-c.3704G N A). Login to comment