ABCC7 p.Ala357Thr
| Predicted by SNAP2: | C: N (61%), D: D (80%), E: D (80%), F: D (80%), G: N (61%), H: D (80%), I: D (53%), K: D (85%), L: D (75%), M: D (53%), N: D (53%), P: D (71%), Q: D (71%), R: D (85%), S: N (82%), T: D (66%), V: D (66%), W: D (85%), Y: D (80%), |
| Predicted by PROVEAN: | C: N, D: D, E: N, F: N, G: N, H: D, I: N, K: N, L: N, M: N, N: D, P: D, Q: N, R: D, S: N, T: N, V: N, W: D, Y: N, |
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[hide] Mutations in the cystic fibrosis transmembrane con... J Cyst Fibros. 2012 Jul;11(4):316-23. doi: 10.1016/j.jcf.2012.01.005. Epub 2012 Apr 6. Li H, Wen Q, Li H, Zhao L, Zhang X, Wang J, Cheng L, Yang J, Chen S, Ma X, Wang B
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) in Chinese patients with congenital bilateral absence of vas deferens.
J Cyst Fibros. 2012 Jul;11(4):316-23. doi: 10.1016/j.jcf.2012.01.005. Epub 2012 Apr 6., [PMID:22483971]
Abstract [show]
BACKGROUND: Genetic testing of the cystic fibrosis transmembrane conductance (CFTR) gene is currently performed in patients with congenital bilateral absence of vas deferens (CBAVD). This study was conducted to investigate the role of mutations in the CFTR gene in CBAVD-dependent male infertility. METHODS: 73 Chinese patients diagnosed with CBAVD were studied. The entire coding regions and splice sites of 27 exons of the CFTR gene were sequenced in 146 chromosomes from the 73 CBAVD patients. Screening was carried out using PCR, gel electrophoresis and DNA sequencing to identify novel variants of the entire coding regions and boundaries of the 27 exons. RESULTS: Five novel nonsynonymous mutations, three novel splice site mutations and one deletion were identified by sequencing. Apart from the novel variants, we also found 19 previously reported mutations and polymorphism sites. Thirty-four patients (46.57%) had the 5T variant (6 homozygous and 28 heterozygous) and in two of them it was not associated with any detectable mutation of the CFTR gene. All potential pathogenic mutations are not contained in the 1000 Genome Project database. In total, the present study identified 30 potential pathogenic variations in the CFTR gene, 9 of which had not previously been described. CONCLUSIONS: Most patients with CBAVD have mutations in the CFTR gene. A mild genotype with one or two mild or variable mutations was observed in all the patients. These findings improve our understanding of the distribution of CFTR alleles in CBAVD patients and will facilitate the development of more sensitive CFTR mutation screening.
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101 In the present study, nine mutations were described for the first time: p.A357T, p.T388K, p.R419I, p.G451K, p.C592F, 870-1 G-C, 1209+1 G-C, 1209+2 T-G, 3635delT.
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ABCC7 p.Ala357Thr 22483971:101:74
status: NEW119 △F508 R117H Mutation genotypes IVS8-Tn n (%) Two mutations detected Neg Neg I556V/I556V 7T/7T 1(1.3) Neg Neg I556V/1209+2 G-C 5T/7T 1(1.3) Neg Neg I556V/726delATT 5T/5T 1(1.3) Neg Neg I556V/- 5T/5T 1(1.3) Neg Neg I556V/- 5T/7T 1(1.3) Neg Neg G970D/- 5T/7T 1(1.3) Neg Neg C592F/- 5T/5T 1(1.3) Neg Neg 1209+1 G-C/- 5T/7T 1(1.3) Neg Neg R553X/- 5T/7T 1(1.3) Neg Neg Q1352H/- 5T/7T 1(1.3) Neg Neg S485C/- 5T/7T 1(1.3) Neg Neg A357T/- 5T/7T 1(1.3) Neg Neg E217G/- 5T/7T 1(1.3) Neg Neg R347H/- 5T/7T 1(1.3) Neg Neg G451K/- 5T/7T 1(1.3) Neg Neg L558S/- 5T/7T 1(1.3) Neg Neg 3635delT/Q1352H 7T/7T 1(1.3) Neg Neg A1136T/G970D 7T/7T 1(1.3) Neg Neg 870-1 G-C/- 5T/7T 1(1.3) Neg Neg 520-2 A-G/- 5T/7T 1(1.3) Neg Neg R419I/- 5T/7T 1(1.3) Neg Neg C491F/Q1643Q 7T/7T 1(1.3) Neg Neg Q1352H/- 5T/7T 1(1.3) Neg Neg R851X/- 5T/7T 1(1.3) Neg Neg P750L/G970D 7T/7T 1(1.3) One mutation detected Neg Neg -/- 5T/7T 2(2.7) Neg Neg -/- 5T/7T 3(4.1) Neg Neg -/- 5T/7T 5(6.8) Neg Neg -/- 5T/5T 2(2.7) Neg Neg -/- 5T/5T 1(1.3) Neg Neg G970D/- 7T/7T 2(2.7) Neg Neg D993Y/- 7T/7T 1(1.3) Neg Neg I556V/- 7T/7T 1(1.3) Neg Neg T388R/- 7T/7T 1(1.3) No mutation detected Neg Neg -/- 7T/7T 8(10.9) Neg Neg -/- 7T/7T 15(20.5) Neg Neg -/- 7T/9T 2(2.7) Neg Neg -/- 7T/7T 4(5.5) Neg: Negative.
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ABCC7 p.Ala357Thr 22483971:119:429
status: NEW121 Mutation Location Nucleotide change Codon change A357T Exon8 G-A at 1069 Ala-Thr T388K Exon9 C-A at 1163 Thr-Lys R419I Exon10 G-T at 1256 Arg-Ile G451K Exon10 G-A at 1351 Gly-Lys C592F Exon14 G-T at 1775 Cys-Phe 870-1 G-C Intron7 Splice error - 1209+1 G-C Intron8 Splice error - 1209+2 T-G Intron8 Splice error - 3635delT Exon22 Frameshift - with CBAVD from the Croatian population had the polythymidine variant 5T [46].
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ABCC7 p.Ala357Thr 22483971:121:49
status: NEW100 In the present study, nine mutations were described for the first time: p.A357T, p.T388K, p.R419I, p.G451K, p.C592F, 870-1 G-C, 1209+1 G-C, 1209+2 T-G, 3635delT.
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ABCC7 p.Ala357Thr 22483971:100:74
status: NEW118 b3;F508 R117H Mutation genotypes IVS8-Tn n (%) Two mutations detected Neg Neg I556V/I556V 7T/7T 1(1.3) Neg Neg I556V/1209+2 G-C 5T/7T 1(1.3) Neg Neg I556V/726delATT 5T/5T 1(1.3) Neg Neg I556V/- 5T/5T 1(1.3) Neg Neg I556V/- 5T/7T 1(1.3) Neg Neg G970D/- 5T/7T 1(1.3) Neg Neg C592F/- 5T/5T 1(1.3) Neg Neg 1209+1 G-C/- 5T/7T 1(1.3) Neg Neg R553X/- 5T/7T 1(1.3) Neg Neg Q1352H/- 5T/7T 1(1.3) Neg Neg S485C/- 5T/7T 1(1.3) Neg Neg A357T/- 5T/7T 1(1.3) Neg Neg E217G/- 5T/7T 1(1.3) Neg Neg R347H/- 5T/7T 1(1.3) Neg Neg G451K/- 5T/7T 1(1.3) Neg Neg L558S/- 5T/7T 1(1.3) Neg Neg 3635delT/Q1352H 7T/7T 1(1.3) Neg Neg A1136T/G970D 7T/7T 1(1.3) Neg Neg 870-1 G-C/- 5T/7T 1(1.3) Neg Neg 520-2 A-G/- 5T/7T 1(1.3) Neg Neg R419I/- 5T/7T 1(1.3) Neg Neg C491F/Q1643Q 7T/7T 1(1.3) Neg Neg Q1352H/- 5T/7T 1(1.3) Neg Neg R851X/- 5T/7T 1(1.3) Neg Neg P750L/G970D 7T/7T 1(1.3) One mutation detected Neg Neg -/- 5T/7T 2(2.7) Neg Neg -/- 5T/7T 3(4.1) Neg Neg -/- 5T/7T 5(6.8) Neg Neg -/- 5T/5T 2(2.7) Neg Neg -/- 5T/5T 1(1.3) Neg Neg G970D/- 7T/7T 2(2.7) Neg Neg D993Y/- 7T/7T 1(1.3) Neg Neg I556V/- 7T/7T 1(1.3) Neg Neg T388R/- 7T/7T 1(1.3) No mutation detected Neg Neg -/- 7T/7T 8(10.9) Neg Neg -/- 7T/7T 15(20.5) Neg Neg -/- 7T/9T 2(2.7) Neg Neg -/- 7T/7T 4(5.5) Neg: Negative.
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ABCC7 p.Ala357Thr 22483971:118:428
status: NEW120 Mutation Location Nucleotide change Codon change A357T Exon8 G-A at 1069 Ala-Thr T388K Exon9 C-A at 1163 Thr-Lys R419I Exon10 G-T at 1256 Arg-Ile G451K Exon10 G-A at 1351 Gly-Lys C592F Exon14 G-T at 1775 Cys-Phe 870-1 G-C Intron7 Splice error - 1209+1 G-C Intron8 Splice error - 1209+2 T-G Intron8 Splice error - 3635delT Exon22 Frameshift - with CBAVD from the Croatian population had the polythymidine variant 5T [46].
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ABCC7 p.Ala357Thr 22483971:120:49
status: NEW[hide] Assessment of epithelial sodium channel variants i... J Cyst Fibros. 2015 Apr 17. pii: S1569-1993(15)00101-0. doi: 10.1016/j.jcf.2015.04.001. Brennan ML, Pique LM, Schrijver I
Assessment of epithelial sodium channel variants in nonwhite cystic fibrosis patients with non-diagnostic CFTR genotypes.
J Cyst Fibros. 2015 Apr 17. pii: S1569-1993(15)00101-0. doi: 10.1016/j.jcf.2015.04.001., [PMID:25900089]
Abstract [show]
PURPOSE: Several lines of evidence suggest a role for the epithelial sodium channel (ENaC) in cystic fibrosis (CF). The purpose of our study was to assess the contribution of genetic variants in the ENaC subunits (alpha, beta, gamma) in nonwhite CF patients in whom CFTR molecular testing has been non-diagnostic. METHODS: Samples were obtained from patients who were nonwhite and whose molecular CFTR testing did not identify two mutations. Sequencing of the SCNN1A, B, and G genes was performed and variants assessed for pathogenicity and association with CF using databases, protein and splice site mutation analysis software, and literature review. RESULTS: We identified four nonsynonymous amino acid variants in SCNN1A, three in SCNN1B and one in SCNN1G. There was no convincing evidence of pathogenicity. Whereas all have been reported in the dbSNP database, only p.Ala334Thr, p.Val573Ile, and p.Thr663Ala in SCNN1A, p.Gly442Val in SCNN1B and p.Gly183Ser in SCNN1G were previously reported in ENaC genetic studies of CF or CF-like patients. Synonymous substitutions were also observed but novel synonymous variants were not detected. CONCLUSION: There is no conclusive association of ENaC genetic variants with CF in nonwhite CF patients.
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44 Ethnicity # of subjectsa SCNN1 subunit Genotype/clinical characteristicsb Sequence variantc Caucasian (France) [26] 56 B Two CFTR mutations; Classic CF p.Thr313Met, p.Gly589Ser G p.Leu481Gln, p.Val546Ile Caucasian (Europe) [28] 29; 47 A One/no CFTR mutation; typical and atypical CF cases c.-760ANG, c.-717GNC, c.-68CNT, p.Pro33Pro p.Phe61Leu, p.Val114Ile, p.Leu180Leu, p.Arg181Trp, p.Ala334Thr, p.Trp493Arg, p.Thr663Ala B p.Ser82Cys, p.Pro93Pro, c.777-5TNC, p.Phe293Phe, p.Ile515Ile, p.Gly589Ser, p.Asp629Asp G p.Tyr129Tyr, p.Ile158Ile, p.Gly183Gly, p.Glu197Lys, c.1176+14ANG, c.1373+29TNC, c.1432-7GNA, p.Leu649Leu Unknown (USA) [23] 20 A No CFTR mutations p.Arg181Trp B Non-classic CF p.Glu539Lys, c.1543-2ANG African 5; 55 (Rwanda) [27] A One/no CFTR mutation; CF-like c.-28TNC, p.Val573Ile B p.Val348Met, p.Gly442Val, p.Thr577Thr, c.1346+28CNT G p.Ser212Ser, c.1176+30GNC Caucasian (Spain) [29] 10 A One/no CFTR mutation; CF and CF-like p.Val14Gly, p.Leu203Leu, p.Arg204Trp, p.Ala304Pro, p.Ala357Thr, p.Cys641Phe, c.875+35GNA B p.Phe293Phe, p.Arg563Gln, p.Pro574Pro G p.Gly183Gly Caucasian/African (France) [24] 20; 35 B One/no CFTR mutation p.Ser82Cys, p.Asn288Ser,p.Pro369Thr G Bronchiectasis p.Gly183Ser, p.Glu197Lys Caucasian (Italy) [35] 24; 15 A One/no CFTR mutation; CFTR-related disorders c.-760ANG, p.Ala334Thr, p.Thr663Ala B p.Pro93Pro, p.Phe293Phe G p.Tyr129Tyr, p.Ile158Ile, p.Gly183Gly, p.Leu649Leu, c.1176+14ANG, c.1373+29TNC, c.1432-7GNA a Listed as number of subjects per genotype (if known).
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ABCC7 p.Ala357Thr 25900089:44:995
status: NEW