ABCMdb

ABCC7 p.Ser158Asn

ClinVar:	c.473G>C , p.Ser158Thr ? , not provided c.472A>C , p.Ser158Arg ? , not provided
CF databases:	c.472A>C , p.Ser158Arg (CFTR1) ? , This substitution involves a residue conserved among species and is located in an intracellular loop of the CFTR protein and affects its charge. We report it as a putative mutation. It was found in a CBAVD patient. No other mutation was detected after analysis of 19 coding regions by DGGE analysis and screening for 3849+10kbC>T and 1811+1.6kbA>G (5 coding regions and splice remain to be analysed). c.473G>A , p.Ser158Asn (CFTR1) ? , This Heterozygous change has been found in an Indian Patient with Chronic Pancreatitis. c.473G>C , p.Ser158Thr (CFTR1) ? , This mutation was seen in 1 out of 96 random samples
Predicted by SNAP2:	A: N (87%), C: N (57%), D: N (87%), E: N (72%), F: D (71%), G: N (93%), H: N (87%), I: D (71%), K: N (72%), L: D (71%), M: D (63%), N: N (97%), P: N (61%), Q: N (82%), R: N (66%), T: N (93%), V: D (66%), W: D (75%), Y: N (57%),
Predicted by PROVEAN:	A: N, C: D, D: D, E: D, F: D, G: N, H: D, I: D, K: D, L: D, M: D, N: N, P: D, Q: D, R: D, T: N, V: D, W: D, Y: D,

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[hide] Cystic fibrosis: S158N (605G --> A) is a rare gene... Genet Test. 2003 Spring;7(1):73-6. Hicks K, Beadling W, Shrimpton AE
Cystic fibrosis: S158N (605G --> A) is a rare genetic variant found in coupling with deltaF508.
Genet Test. 2003 Spring;7(1):73-6., [PMID:12820707]

Abstract [show]
A single nucleotide change at codon 158 in exon 4 of the CFTR gene ABCC7 was detected in an asymptomatic individual who carried deltaF508 and had a family history of cystic fibrosis (CF). Further study, using linkage, revealed that S158N was coupled with deltaF508, both having been inherited from the same parent. The clinical implications of double mutations in the same allele are discussed.

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No. Sentence Comment
1 Cystic Fibrosis: S158N (605G R A) Is a Rare Genetic Variant Found in Coupling with DF508 KAREN HICKS, WENDY BEADLING, and ANTONY E. SHRIMPTON ABSTRACT A single nucleotide change at codon 158 in exon 4 of the CFTR gene ABCC7 was detected in an asymptomatic individual who carried DF508 and had a family history of cystic fibrosis (CF). Login to comment
2 Further study, using linkage, revealed that S158N was coupled with DF508, both having been inherited from the same parent. Login to comment
22 This transition of a G to A occurs at nucleotide 605; the second nucleotide of codon 158, is predicted to result in the substitution of an asparagine (AAT) for a serine (AGT), hence the designation S158N. Login to comment
23 Follow-up testing on the patient`s parents and affected sibling surprisingly showed that S158N and DF508 were in coupling, having been inherited from the same parent (Fig. 4). Login to comment
29 To our surprise, we found that the new mutation, S158N, was coupled with DF508. Login to comment
31 Thus, we describe S158N as a rare genetic variant. Login to comment
40 Serine to asparagineat codon158: S158N (605G R A). Login to comment
42 CF: S158N (605G R A). Login to comment
48 Additional studies will be needed to determine whether S158N is such a modifying mutation, a primary pathologic mutation, or a benign variant. Login to comment
49 If the S158N/DF508 genotype had first been detected in the CF-affected child, rather than as in this case, in an unaffected sibling, how often would a family study to determine linkage have been initiated? Login to comment

[hide] Identification and characterization of CFTR gene m... Ann Hum Genet. 2009 Jan;73(1):26-33. Epub 2008 Sep 8. Sharma N, Singh M, Kaur G, Thapa BR, Prasad R
Identification and characterization of CFTR gene mutations in Indian CF patients.
Ann Hum Genet. 2009 Jan;73(1):26-33. Epub 2008 Sep 8., [PMID:18782298]

Abstract [show]
Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This study was performed on Indian CF patients (n = 50) to investigate the spectrum of mutations in the CFTR gene and their association with intragenic and extragenic marker haplotypes. We report identification of 14 previously known and eight novel mutations, namely 3986-3987delC, 876-6del4, 1792InsA, L69H, S158N, Q493L, I530L and E1329Q. The frequency of delta F508 was found to be 27%. Absolute linkage between delta F508 and the KM.19-GATT-TUB9-M470V-T854T haplotype (2-2-1-1-1) predicts a relatively recent appearance of delta F508 in Indian CF patients. Low frequency of delta F508 mutation and detection of eight novel and thirteen rare mutations reflect a heterogeneous spectrum of mutations in Indian CF patients. Failure to detect mutations in 34% of alleles indicates the possible presence of gross deletions involving one or more exons or may indicate the location of the molecular defects in either the noncoding parts of the gene or in the promoter region, which warrants analysis of those regions.

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No. Sentence Comment
2 We report identification of 14 previously known and eight novel mutations, namely 3986-3987delC, 876-6del4, 1792InsA, L69H, S158N, Q493L, I530L and E1329Q. Login to comment
67 They included nine missense mutations (L69H, S158N, Q493L, Y517C, V520F, I530L, S549N, E1329Q, and Y1381H), one insertion mutation (1792insA), three splice site mutations (876-6del4, 1525-1G-A, 3120+1G-A), two deletion mutations (1161delC, 3986delC), and 1 nonsense mutation (L218X). Login to comment
73 Novel Mutations and Phenotypic Features Output prediction scores were assessed for five novel mutations; they were >0.5 for L69H & Q493L and <0.5 for S158N, I530L & E1329Q (Table 3). Login to comment
79 S158N The chief complaint of the 13 yr old patient, compound heterozygous for S158N, was recurrent coughs for the last five years. Login to comment
96 Table 2 Genotypes of CF subjects (n=50) Genotype Number of subjects Delta F508/Delta F508 5 Delta F508/3849+10kb C-T 1 Delta F508/S549N 2 Delta F508/S158N 1 Delta F508/Y1381H 1 Delta F508/1525-1 G-A 2 V520F/R117H 1 I530L/I530L 1 876-6del4/876-6del4 1 1792ins A/1792insA 1 3986-3987delC/3986-3987delC 1 Delta F508/U 10 1161 delC/U 2 L69H/U 1 R117H/U 1 Q493L/U 1 Y517C/U 1 S549N/U 3 G551D/U 1 E1329Q/U 1 N1303K/U 1 Y1381H/U 1 L218X/U 1 R553X/U 1 1525-1G-A/U 3 3120+1G-A/U 2 3849+10kb C-T/U 2 U/U 1 U-unidentified Table 3 Outcome prediction scores of novel substitution mutations identified in Indian CF patients Wild type Mutant Position Output Reliablity Prediction L H 69 0.5210 0 Pathological S N 158 0.3304 3 Neutral Q L 493 0.7784 5 Pathological I L 530 0.0591 8 Neutral E Q 1329 0.1018 7 Neutral Molecular Modelling and Bioinformatics (MMB) program (http://mmb.pcb.ub.es/PMut/) was used for pathological predictions of novel sequence variants. Login to comment
113 We first identified five of the mutations by ARMS (Delta F508, R117H, R553X, N1303K & G551D) and one by restriction digestion (3849+10kbC-T) and later identified by SSCP eight known (Y517C, V520F, S549N, Y1381H, 1525-1G-A, 3120+1G-A, 1161delC and L218X) and eight previously unreported mutations (L69H, S158N, Q493L, I530L, E1329Q, 876-6del4, 1792insA and 3986-3987delC). Login to comment
133 Output prediction scores deduced using molecular modeling and a bioinformatics program (http://mmb.pcb.ub.es/PMut/) revealed that among the novel mutations, L69H and Q493L are pathologic but S158N, I530L and E1329Q are neutral. Login to comment

[hide] Molecular basis of cystic fibrosis disease: an Ind... Indian J Clin Biochem. 2010 Oct;25(4):335-41. Epub 2010 Nov 19. Prasad R, Sharma H, Kaur G
Molecular basis of cystic fibrosis disease: an Indian perspective.
Indian J Clin Biochem. 2010 Oct;25(4):335-41. Epub 2010 Nov 19., [PMID:21966101]

Abstract [show]
Cystic fibrosis is a common autosomal recessive disorder usually found in population of white Caucasian descent. Now it is well documented the presence of CF disease in India with the advancement of laboratory testing. As once it was thought non existence of this disease in our population. Most of the phenotype of CF disease was in accordance of western population. Genetic analysis of CFTR gene in Indian CF patients revealed that most common mutation was delta F508 mutation. However, it was less than Caucasian population. CFTR mutations are also a causative factor in the pathogenesis of male infertility due to obstructive azoospermia. There are two most common mutation viz. IVS8-T5 and delta F508 which are responsible for congenital absence of vas deferens in male infertility patients. Elevated levels of sweat chloride at two occasions along with the presence of two mutations in CFTR gene was gold standard method for diagnosis of CF disease. It is noteworthy here that due to magnitude of Indian population, the total CF disease load would be more than many European countries. Clinical data demonstrate the prevalence of both classical and genetic form of CF in India.

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99 The other seven known but rare mutations (1161delC, Y517C, V520F, S549N, Y1381H, L218X and 1525-1G-A) were identified at a combined frequency of (17%), and eight new mutations (3986delC, 1792InsA, L69H, S158N, Q493L, I530L, E1329Q and 876-8del4) identified in our CF population represented (15%) of the total CF alleles analyzed. Login to comment