ABCC7 p.Val322Ala
| ClinVar: |
c.964G>A
,
p.Val322Met
?
, Uncertain significance
|
| CF databases: |
c.965T>C
,
p.Val322Ala
(CFTR1)
?
, A novel allele was identified by DGGE and direct sequencing. As this nucleotide change was identified through a neonatal screening program we have no arguments to consider it as a polymorphism or a mutation
|
| Predicted by SNAP2: | A: D (80%), C: D (75%), D: D (95%), E: D (91%), F: D (75%), G: D (95%), H: D (95%), I: N (57%), K: D (95%), L: D (80%), M: N (66%), N: D (91%), P: D (95%), Q: D (95%), R: D (95%), S: D (85%), T: D (91%), W: D (95%), Y: D (95%), |
| 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, |
[switch to compact view]
Comments [show]
None has been submitted yet.
[hide] Prevalence of CFTR mutations in hypertrypsinaemia ... Clin Genet. 2001 Jan;59(1):42-7. Scotet V, De Braekeleer M, Audrezet MP, Lode L, Verlingue C, Quere I, Mercier B, Dugueperoux I, Codet JP, Moineau MP, Parent P, Ferec C
Prevalence of CFTR mutations in hypertrypsinaemia detected through neonatal screening for cystic fibrosis.
Clin Genet. 2001 Jan;59(1):42-7., [PMID:11168024]
Abstract [show]
Nowadays, most of the neonatal screening programs for cystic fibrosis (CF) combine the assay of immunoreactive trypsinogen (IRT) with the analysis of the most common mutations of the CFTR gene. The efficiency of this strategy is now well established, but the identification of heterozygotes among neonates with increased IRT is perceived as a drawback. We proposed to assess the heterozygosity frequency among the children with hypertrypsinaemia detected through the CF screening program implemented in Brittany (France) 10 years ago, to describe the CFTR mutations detected in them and to determine the frequency of the IVS8-5T variant. The molecular analysis relies, in our protocol, on the systematic analysis of three exons of the gene (7-10-11). A total of 160,019 babies were screened for CF in western Brittany between 1992 and 1998. Of the 1964 newborns with increased IRT (1.2%), 60 were CF and 213 were carriers. Heterozygosity frequency was 12.8%), i.e. 3 times greater than in the general population (3.9%; p < 10(-6)), Variability of mutations detected in carriers was greater than in CF children (21 mutations versus 10) and a high proportion of mild mutations or variants (A349V, R297Q, R347H, V317A, G544S, R553G, etc) was observed in carriers. The allelic frequency of the 5T (5.6%) was not significantly increased in this cohort. This study is consistent with previous ones in finding a significantly higher rate of heterozygotes than expected among neonates with hypertrypsinaemia. The strategy of screening used here allows to highlight the variability of mutations detected in heterozygotes and to show that severe mutations, as well as mild mutations, have been observed in neonates with hypertrypsinaemia. If there is no doubt that neonatal hypertrypsinaemia is associated with an elevated frequency of carriers, the underlying mechanisms remain obscure.
Comments [show]
None has been submitted yet.
No. Sentence Comment
74 We noted, among heterozygous children, a high proportion of mild mutations (R297Q, R347H, M348K, A349V, G544S) or for which the pathogenicity is yet impossible to determine (V317A, V322A, R553G).
X
ABCC7 p.Val322Ala 11168024:74:181
status: NEW89 Molecular abnormalities detected in exons 7, 10 and 11 of the CFTR gene in a control population and in the affected and heterozygous children identified by the neonatal screening between 1992 and 1998 in Brittany, France ContributorsAlleles in the controlAlleles in affectedMolecular abnormalities Alleles in carrierExon Type children populationchildren No % No % No % Disease causing mutations Y301C 7 Mild 1 0.47 Constantinou-Deltas CD et al.* 7 Mild 1 1.03 9 4.22 Cremonesi L et al. (38)R347H Audre´zet MP et al. (39)0.471Mild7M348K 7 MildA349V 1 0.47 Audre´zet MP et al. (30) Fe´rec C et al. (29)0.471Mild10S492F 0.942 This studyMild11G544S 11 MildI556V 1 0.47 Ghanem N et al.* R560K 11 Mild 1 0.47 Fe´rec C et al. (29) 1078delT 7 Severe 2 2.06 5 2.35 Claustres M et al. (40) Fe´rec C et al. (29)0.471Severe71221delCT DF508 10 Severe 81 83.51 170 79.81 11 2.6 Kerem B et al. (12) DI507 Schwarz M et al. (41)0.471Severe10 11 Severe1717-1 GA 1 1.03 3 1.41 Kerem B et al. (42) Scotet V et al. (28)1.0311806delA 11 Severe Kerem B et al. (42)1.8743.09G542X 11 Severe 3 5.16 5 2.35 Cutting GR et al. (43)G551D 11 Severe 5 Cutting GR et al. (43)1 0.471.03R553X 11 Severe 1 Non-disease causing mutations R297Q 7 1 1.03 1 0.47 Graham CA et al.* 0.942 This study7V317A V322A 7 1 0.47 This study 11 1 1.03 1 0.47 Scotet V et al. (28)R553G 11R553Q 1 0.47 Dork T et al. (44) 97 100 213 100 422 100 * From Cystic Fibrosis Genetic Analysis Consortium (http://www.genet.sickkids.on.ca) An excess of heterozygotes carrier of the most frequent mutation (DF508) among neonates with hypertrypsinaemia has been reported (23, 24).
X
ABCC7 p.Val322Ala 11168024:89:1294
status: NEW[hide] Direct comparison of the functional roles played b... J Biol Chem. 2004 Dec 31;279(53):55283-9. Epub 2004 Oct 25. Ge N, Muise CN, Gong X, Linsdell P
Direct comparison of the functional roles played by different transmembrane regions in the cystic fibrosis transmembrane conductance regulator chloride channel pore.
J Biol Chem. 2004 Dec 31;279(53):55283-9. Epub 2004 Oct 25., 2004-12-31 [PMID:15504721]
Abstract [show]
The cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel contains 12 transmembrane (TM) regions that are presumed to form the channel pore. However, little is known about the relative functional contribution of different TM regions to the pore. We have used patch clamp recording to investigate the functional consequences of point mutations throughout the six transmembrane regions in the N-terminal part of the CFTR protein (TM1-TM6). A range of specific functional assays compared the single channel conductance, anion binding, and anion selectivity properties of different channel variants. Overall, our results suggest that TM1 and -6 play dominant roles in forming the channel pore and determining its functional properties, with TM5 perhaps playing a lesser role. In contrast, TM2, -3, and -4 appear to play only minor supporting roles. These results define transmembrane regions 1 and 6 as major contributors to the CFTR channel pore and have strong implications for emerging structural models of CFTR and related ATP-binding cassette proteins.
Comments [show]
None has been submitted yet.
No. Sentence Comment
77 Significant, but smaller, reductions in unitary conductance were observed in G213A, V318A, S321A, V322A, K335A, and I336A (Figs. 3 and 4).
X
ABCC7 p.Val322Ala 15504721:77:98
status: NEW[hide] Neonatal screening for cystic fibrosis: result of ... Hum Genet. 1995 Nov;96(5):542-8. Ferec C, Verlingue C, Parent P, Morin JF, Codet JP, Rault G, Dagorne M, Lemoigne A, Journel H, Roussey M, et al.
Neonatal screening for cystic fibrosis: result of a pilot study using both immunoreactive trypsinogen and cystic fibrosis gene mutation analyses.
Hum Genet. 1995 Nov;96(5):542-8., [PMID:8530001]
Abstract [show]
We have evaluated a two-tier neonatal cystic fibrosis (CF) screening of immunoreactive trypsinogen (IRT) followed by CFTR gene mutation analysis using a systematic scanning of exons 7, 10, and 11, and, if necessary, by direct DNA sequencing. Over an 18-month period we screened 32,300 neonates born in the western part of Britanny. The first tier, involving IRT screening at 3 days of age, utilizes a low elevation of the trypsinogen level (600 ng/ml), which is highly sensitive. The second tier, which corresponds to the exhaustive screening for mutations in three exons of the gene, is highly specific for this population (Britanny). The false positive rate is very low, and no false negatives have been reported to date. This strategy has allowed the identification of five novel alleles (V322A, V317A, 1806 del A, R553G, G544S).
Comments [show]
None has been submitted yet.
No. Sentence Comment
5 This strategy has allowed the identification of five novel alleles (V322A, V317A, 1806 del A, R553G, G544S).
X
ABCC7 p.Val322Ala 8530001:5:68
status: NEW82 {17bi DI507 [ Y569X W846X 2789+5G->A ,' $492F i ] i I G551D 2622+1 G->A Y1092X 1717-1 G->A E827X A1067T G542X 2183 AA->G R1066H R560K 2184 ins A 3320,ins 5 R553G R1070W 1806 del A & 4005+1G->A W1282X ] i "- Exons Fig.2 Distribution of the different mutations (except AF508) of the CFTR gene in Brittany Table 1 Mutations and genotypes in newborns Genotypes of newborns Number Sweat test AF508/AF508 7 + > 90 AF508/1806 del A 1 + > 90 R553G/G551D 1 Borderline (60) AF508/G551D 1 + > 90 AF508/R1070W 1 40 AF508/G542X 1 + > 90 AF508/G149R 1 45 Total 13 Mutations found in heterozygote newborns AF508 31 R560K 1 1078 del T 1 G544S l G542X 1 V317A 1 R347H 1 V322A 1 Total 38 gene.
X
ABCC7 p.Val322Ala 8530001:82:653
status: NEW87 The second molecular abnormality found was a T----)C change at position 1097 in exon 7 also resulting in a valine to alanine substitution (V322A).
X
ABCC7 p.Val322Ala 8530001:87:139
status: NEW128 The other mutations whose pathogenicity is, as yet, impossible to determine are V322A, V317A, and G544S.
X
ABCC7 p.Val322Ala 8530001:128:82
status: NEW