ABCC7 p.Val1212Ile
| ClinVar: |
c.3634G>A
,
p.Val1212Ile
?
, not provided
|
| CF databases: |
c.3634G>A
,
p.Val1212Ile
(CFTR1)
D
, The V1212I mutation was detected as a second alteration in two Czech CF siblings who are [delta]F508 homozygotes. ASO analysis of 171 non-CF chromosomes did not detect this mutation on any tested chromosomes.
c.3634G>T , p.Val1212Phe (CFTR1) ? , |
| Predicted by SNAP2: | A: N (57%), C: N (78%), D: D (75%), E: D (66%), F: N (87%), G: D (66%), H: D (66%), I: N (97%), K: D (75%), L: N (93%), M: N (87%), N: D (53%), P: D (66%), Q: D (63%), R: D (75%), S: D (59%), T: D (53%), W: D (71%), Y: N (61%), |
| Predicted by PROVEAN: | A: N, C: N, D: D, E: D, F: N, G: D, H: N, I: N, K: D, L: N, M: N, N: D, P: D, Q: D, R: D, S: N, T: N, W: N, Y: N, |
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[hide] Two mild cystic fibrosis-associated mutations resu... J Biol Chem. 2001 Mar 23;276(12):9045-9. Epub 2000 Dec 15. Clain J, Fritsch J, Lehmann-Che J, Bali M, Arous N, Goossens M, Edelman A, Fanen P
Two mild cystic fibrosis-associated mutations result in severe cystic fibrosis when combined in cis and reveal a residue important for cystic fibrosis transmembrane conductance regulator processing and function.
J Biol Chem. 2001 Mar 23;276(12):9045-9. Epub 2000 Dec 15., 2001-03-23 [PMID:11118444]
Abstract [show]
The number of complex cystic fibrosis transmembrane conductance regulator (CFTR) genotypes identified as having double-mutant alleles with two mutations inherited in cis has been growing. We investigated the structure-function relationships of a severe cystic fibrosis (CF)-associated double mutant (R347H-D979A) to evaluate the contribution of each mild mutation to the phenotype. CFTR mutants expressed in HeLa cells were analyzed for protein biosynthesis and Cl(-) channel activity. Our data show that R347H is associated with mild defective Cl(-) channel activity and that the D979A defect leads to misprocessing. The mutant R347H-D979A combines both defects for a dramatic decrease in Cl(-) current. To decipher the molecular mechanism of this phenotype, single and double mutants with different charge combinations at residues 347 and 979 were constructed as charged residues were involved in this complex genotype. These studies revealed that residue 979, located in the third cytoplasmic loop, is critical for CFTR processing and Cl(-) channel activity highlighting the role of charged residues. These results have also important implications for CF, as they show that two mutations in cis can act in concert to alter dramatically CFTR function contributing to the wide phenotypic variability of CF disease.
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No. Sentence Comment
125 DISCUSSION Complex alleles have been described clinically (R553Q- ⌬F508, ⌬F508-V1212I, and R334W-R1158X), and most of them are considered to reverse the phenotype, as they are associated with milder symptoms than the most common mutation in isolation.
X
ABCC7 p.Val1212Ile 11118444:125:93
status: NEW[hide] Complex cystic fibrosis allele R334W-R1158X result... Hum Mutat. 1996;8(2):134-9. Duarte A, Amaral M, Barreto C, Pacheco P, Lavinha J
Complex cystic fibrosis allele R334W-R1158X results in reduced levels of correctly processed mRNA in a pancreatic sufficient patient.
Hum Mutat. 1996;8(2):134-9., [PMID:8844211]
Abstract [show]
CFTR alleles containing two mutations have been very rarely found in cystic fibrosis (CF) patients. They provide an opportunity to study the effect of two in cis-interacting gene defects on gene expression. Here, we describe a three-generation CF family with a complex CFTR allele that has not been previously described, containing the missense mutation R334W in exon 7 and the nonsense mutation R1158X in exon 19. Lymphocyte RNA analysis showed that (1) the mRNA corresponding to the complex allele is present although at markedly reduced levels; and (2) the nonsense mutation does not lead to detectable skipping of exon 19. The clinical picture of the patients with the genotype R334W-R1158X/delta F508 is characterized by pancreatic sufficiency and an atypical course of the disease.
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No. Sentence Comment
37 The first published complex allele in the CFTR gene (Dork et al., 1991) consisted of an alteration (R553Q) that partially reverted the phenotypic effects of the AF508 mutation (Teem et al., 1993).The sameseems to apply to the AF508- V1212I allele (Macek et al., 1993).
X
ABCC7 p.Val1212Ile 8844211:37:233
status: NEW[hide] Laboratory tests for the diagnosis of cystic fibro... Am J Clin Pathol. 2002 Jun;117 Suppl:S109-15. Wang L, Freedman SD
Laboratory tests for the diagnosis of cystic fibrosis.
Am J Clin Pathol. 2002 Jun;117 Suppl:S109-15., [PMID:14569807]
Abstract [show]
Cystic fibrosis (CF) remains the most common life-limiting inherited disease in America. Making an accurate, early diagnosis is essential to the management of the disease. The diagnostic criteria for CF require the presence of 1 or more typical clinical features, a family history of CF, or a positive newborn screening test, plus laboratory evidence of the CF transmembrane conductance regulator (CFTR) dysfunction. In the past, the laboratory test of abnormal CFTR function was based largely on an elevated sweat chloride test result. The recent development of a genotypic CFTR mutation screen has greatly improved diagnostic accuracy. Increased screening of the CFTR locus has led to the recognition of a number of atypical CF disorders. Recently, a 2-tiered newborn screening protocol including CFTR genotyping has become popular, increasing the likelihood of early diagnosis.
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No. Sentence Comment
67 For example, the complex allele R553Q-delta F508 has been shown to revert partially or ameliorate the phenotype of delta F508 mutation.15 Other revertants (delta F508-V1212I and R334W-R1158X) associated with mild or atypical CF have also been described.16,17 Nasal Potential-Difference Measurements This is a functional test for the CFTR gene product.
X
ABCC7 p.Val1212Ile 14569807:67:167
status: NEW