ABCMdb

PMID: 22326559

Poulou M, Fylaktou I, Fotoulaki M, Kanavakis E, Tzetis M
Cystic fibrosis genetic counseling difficulties due to the identification of novel mutations in the CFTR gene.
J Cyst Fibros. 2012 Jul;11(4):344-8. doi: 10.1016/j.jcf.2012.01.004. Epub 2012 Feb 11., [PubMed]

Sentences

No. Mutations Sentence Comment

37 ABCC7 p.Leu541Pro ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys The azoospermic male (case 3) (sweat chloride test 90 meq/L) was compound heterozygote for p.Asn1303Lys [N1303K] and the novel variant p.Leu541Pro, in trans, described as pathogenic by the four in silico methods, and predicted to alter enhancer and silencer motifs (Table 2). Login to comment 38 ABCC7 p.Leu541Pro In this case we can conclude that p.Leu541Pro in combination with a severe mutation will result in a CFTR-related phenotype. Login to comment 59 ABCC7 p.Leu541Pro ABCC7 p.Asn1303Lys ABCC7 p.Gln378Arg ABCC7 p.Pro936Thr Case Exon or intron (legacy) Nucleotide change Mutation Other findings Polyphen-2 SIFT Pmut Mutation T@sting Phenotype 1 4 (4) c.405_406dupAC p.Leu136HisfsX18 p.F508del (in trans) N/A N/A N/A Disease causing Classic CF 2 23 (20) c.3815_3816delTG p.Ser1273LeufsX28 p.F508del (in trans) N/A N/A N/A Disease causing Classic CF 3 12 (11) c.1622TNC p.Leu541Pro p.N1303K (in trans) Prob. Dam. NT 0.00 Path. (6) Disease causing Azoospermia 4 17 (15) c.2806CNA p.Pro936Thr p.L1227L Prob. Dam. NT 0.03 Path. (4) Disease causing Inadequate weight gain 5 9 (8) c.1133ANG p.Gln378Arg Prob. Dam. T 0.11 Neut. Login to comment 60 ABCC7 p.Ser945Tyr ABCC7 p.Met595Val (6) Disease causing Screening 6 11 (10) c.1484CNA p.Ser945Tyr Prob. Dam. NT 0.00 Path. (2) Disease causing Screening 7 1 (1) c.2TNG p.Met1Arg Prob. Dam. NT 0.00 Path. (7) Disease causing Asthma 8 14 (11) c.1783ANG p.Met595Val Prob. Dam. NT 0.02 Neut. Login to comment 61 ABCC7 p.Lys1165Thr ABCC7 p.Val1318Gly ABCC7 p.Ile521Phe ABCC7 p.Val1212Phe ABCC7 p.Phe319Val ABCC7 p.Ser977Cys (2) Disease causing Screening 9 24 (21) c.3953TNG p.Val1318Gly Prob. Dam. NT 0.00 Path. (8) Disease causing Azoospermia 10 22 (19) c.3494ANC p.Lys1165Thr Poss. Dam. NT 0.04 Path. (8) Disease causing Bronchitis 11 18 (15) c.2930CNG p.Ser977Cys Poss. Dam. NT 0.01 Path. (5) Disease causing Screening 12 11 (10) c.1561ANT p.Ile521Phe Poss. Dam. NT 0.01 Path. (0) Disease causing CBAVD 13 22 (19) c.3634GNT p.Val1212Phe Poss. Dam. T 0.42 Path. (6) Disease causing Screening 14 8 (7) c.955TNG p.Phe319Val Poss. Dam. T 0.48 Neut. Login to comment 62 ABCC7 p.Cys491Ser ABCC7 p.Gly817Val (3) Disease causing Atypical CF 15 14 (13) c.2450GNT p.Gly817Val Benign T 0.31 Path. (4) Polymorphism CBAVD 16 11 (10) c.1472GNC p.Cys491Ser Benign T 0.59 Neut. Login to comment 63 ABCC7 p.Ile336Leu (3) Disease causing CBAVD 17 8 (7) c.1006ANC p.Ile336Leu Prob. Dam. T 0.19 Neut. Login to comment 64 ABCC7 p.Phe305Val (9) Disease causing Screening 18 8 (7) c.913TNG p.Phe305Val Benign T 0.33 Neut. Login to comment 65 ABCC7 p.Phe533Leu ABCC7 p.Ser511Cys ABCC7 p.Leu926Phe ABCC7 p.Ser1311Asn ABCC7 p.Ala1225Val (2) Disease causing Screening 19 11 (10) c.1532CNG p.Ser511Cys Benign T 0.06 Path. (2) Disease causing Screening 20 24 (21) c.3932GNA p.Ser1311Asn Benign T 0.34 Path. (3) Disease causing Screening 21 17 (15) c.2778GNT p.Leu926Phe Benign T 0.24 Path. (5) Disease causing Screening 22 22 (21) c.3674CNT p.Ala1225Val Benign T0.21 Path. (1) Disease causing Screening 23 12 (11) c.1597TNC p.Phe533Leu Benign T0.94 Neut. Login to comment 66 ABCC7 p.Asp110Glu ABCC7 p.Ser737Phe ABCC7 p.Gln1209His (6) Disease causing Screening 24 22 (19) c.3627ANC p.Gln1209His p.Asp110Glu (in cis) and p.Ser737Phe (in trans) Benign NT 0.02 Path. (5) Disease causing Metabolic alkalosis 25 int14 (13) c.2490+3ANG N/A N/A N/A Polymorphism Screening 26 Int17 (15) c.2909-36TNC N/A N/A N/A Polymorphism Screening 27 int17 (15) c.2909-10TNC N/A N/A N/A Polymorphism Screening 28 int25 (22) c.4137-21GNT N/A N/A N/A Polymorphism Screening 29 int8 (7) c.1116+4ANT N/A N/A N/A Disease causing Screening 30 int18 (16) c.2988+30TNC N/A N/A N/A Polymorphism Screening 31 int12 (11) c.1680-27GNA N/A N/A N/A Polymorphism Screening 32 int15 (14a) c.2620-24CNG N/A N/A N/A Polymorphism Ech. Bowel 33 int15 (14a) c.2620-18delT N/A N/A N/A Polymorphism Screening 34 c.2790-8CNG N/A N/A N/A Obstr. Login to comment 67 ABCC7 p.Pro936Thr Azoosp. 4 22(19) c.3681ANG p.Leu1227Leu p.P936T N/A N/A N/A Polymorphism Inadequate weight gain 35 22(19) c.3472CNA p.Arg1158Arg N/A N/A N/A polymorphism Oligospermia 36 23 (20) c.3825TNC p.Asp1275Asp N/A N/A N/A Polymorphism Malabs. Login to comment 72 ABCC7 p.Leu541Pro ABCC7 p.Gln378Arg ABCC7 p.Pro936Thr ABCC7 p.Ser945Tyr ABCC7 p.Met595Val Mutation Nucleotide change ESEfinder (WT/MUT) HSF (WT/MUT) Mutation T@ster (WT/MUT) p.L541P c.1622TNC Increased score for 5SS_U2_human (3.48/5.16)/increased score for SC35 (3.48/3.89) Creation of ESE motifs/creation and disruption of ESS motifs Donor gained (0.59) p.P936T c.2806CNA Decreased score for 5SS_U2_human (4.07/3.97)/decreased score for SC35 (4.00/2.72) Increased branch point motif (53.55/83.18)/disruption of ESE motifs No change on splice sites p.Q378R c.1133ANG No change Disruption of ESE motifs/creation of ESS motifs Donor gained (0.94) p.S945Y c.1484CNA Change for SRp40 best hit (4.6/5.76) Disruption of ESE motifs/disruption of ESS motifs Donor increased (0.30/0.91) p.M1R c.2TNG Reduced score for SRp55 (4.34/3.51) Disruption of ESE motifs Acceptor lost/donor increased (0.48 /0.56) p.M595V c.1783ANG No change Donor ss increased (46.9/73.74) if used causes exon skipping. Login to comment 73 ABCC7 p.Phe533Leu ABCC7 p.Cys491Ser ABCC7 p.Lys1165Thr ABCC7 p.Val1318Gly ABCC7 p.Val1212Phe ABCC7 p.Phe319Val ABCC7 p.Ser977Cys ABCC7 p.Gly817Val ABCC7 p.Ile336Leu ABCC7 p.Phe305Val ABCC7 p.Ser511Cys ABCC7 p.Leu926Phe ABCC7 p.Ser1311Asn ABCC7 p.Ala1225Val ABCC7 p.Gln1209His Disruption of ESE motifs/creation of ESS motifs Acc increased (0.44/0.50) Acc gained 0.51 p.V1318G c.3953TNG No change New donor site (48.15/74.98) (+55.73%) if used causes reduction of exon size (-11nt) Donor increased (0.31/0.99) p.K1165T c.3494ANC No change Minor changes No change p.S977C c.2930CNG No change Minor changes No change p.I521F c.1561ANT No change Minor changes No change p.V1212F c.3634GNT No change Disruption of ESE motifs Donor gained 0.36 p.F319V c.955TNG No change Minor changes Acc increased (0.42/0.61) p.G817V c.2450GNT No change Minor changes No change p.C491S c.1472GNC No change Disruption of ESE motifs Acceptor sites created p.I336L c.1006ANC No change Disruption of ESE motifs No change p.F305V c.913TNG Increased score for SRp55 Disruption of ESS motifs Donor gained (0.99) p.S511C c.1532CNG Decreased score for SC35 Disruption of ESS motifs No change p.S1311N c.3932GNA Changes on ss scores Disruption of ESS motifs Donor increased (0.50/0.63) p.L926F c.2778GNT No change Creation of ESS motifs Changes on ss scores p.A1225V c.3674CNT No change Disruption of ESE motif/creation of ESS motif Donor increased (0.72/0.99) p.F533L c.1597TNC No change Creation of ESE motifs/disruption of ESS motifs No change p.Q1209H c.3627ANC No change Minor changes No change c.2490+3ANG No change Minor changes No change c.2909-36TNC Decrease of donor ss Disruption of ESS motifs Acc increased (0.33/0.48)/donor increased (0.74/0.94) c.2909-10TNC Change for SRp55 best hit (3.97/5.16) Disruption of ESS motifs No change c.4137-21GNT No change Disruption of ESE and creation of ESS motifs Acc increased (0.86/0.96) c.1116+4ANT No change WT donor site disrupted Marginal changes on donor ss c.2988+30TNC No change Disruption of ESE motif/creation of ESS motif No change c.1680-27GNA No change Disruption of ESS motifs No change c.2620-24CNG No change Creation of ESE motifs Donor gained 0.96 c.2620-18delT No change New donor ss/changes on ESE and ESS motifs Acc increased (0.41/0.55) c.2658-8CNG Decreased score for acc site Minor changes Marginal changes on ss p.L1227L c.3681ANG No change Changes on ESE and ESS motifs No change p.R1158R c.3472CNA No change Creation of ESE motifs/creation of ESS motifs Marginal changes on ss p.D1275D c.3825TNC No change No change Donor increased (0.56/0.87) p.L346L c.1036CNT No change No change No change Abbreviations: ESE: exonic splicing enhancer, HSF: human splicing finder, ESS: exonic splicing silencer, WT: wild type, Mut: mutant, ss: splicing site. Login to comment 74 ABCC7 p.Leu541Pro ABCC7 p.Gln378Arg ABCC7 p.Pro936Thr ABCC7 p.Ser945Tyr ABCC7 p.Met595Val Mutation Nucleotide change ESEfinder (WT/MUT) HSF (WT/MUT) Mutation T@ster (WT/MUT) p.L541P c.1622TNC Increased score for 5SS_U2_human (3.48/5.16)/increased score for SC35 (3.48/3.89) Creation of ESE motifs/creation and disruption of ESS motifs Donor gained (0.59) p.P936T c.2806CNA Decreased score for 5SS_U2_human (4.07/3.97)/decreased score for SC35 (4.00/2.72) Increased branch point motif (53.55/83.18)/disruption of ESE motifs No change on splice sites p.Q378R c.1133ANG No change Disruption of ESE motifs/creation of ESS motifs Donor gained (0.94) p.S945Y c.1484CNA Change for SRp40 best hit (4.6/5.76) Disruption of ESE motifs/disruption of ESS motifs Donor increased (0.30/0.91) p.M1R c.2TNG Reduced score for SRp55 (4.34/3.51) Disruption of ESE motifs Acceptor lost/donor increased (0.48 /0.56) p.M595V c.1783ANG No change Donor ss increased (46.9/73.74) if used causes exon skipping. Login to comment 75 ABCC7 p.Phe533Leu ABCC7 p.Cys491Ser ABCC7 p.Lys1165Thr ABCC7 p.Val1318Gly ABCC7 p.Val1212Phe ABCC7 p.Phe319Val ABCC7 p.Ser977Cys ABCC7 p.Gly817Val ABCC7 p.Ile336Leu ABCC7 p.Phe305Val ABCC7 p.Ser511Cys ABCC7 p.Leu926Phe ABCC7 p.Ser1311Asn ABCC7 p.Ala1225Val ABCC7 p.Gln1209His Disruption of ESE motifs/creation of ESS motifs Acc increased (0.44/0.50) Acc gained 0.51 p.V1318G c.3953TNG No change New donor site (48.15/74.98) (+55.73%) if used causes reduction of exon size (-11nt) Donor increased (0.31/0.99) p.K1165T c.3494ANC No change Minor changes No change p.S977C c.2930CNG No change Minor changes No change p.I521F c.1561ANT No change Minor changes No change p.V1212F c.3634GNT No change Disruption of ESE motifs Donor gained 0.36 p.F319V c.955TNG No change Minor changes Acc increased (0.42/0.61) p.G817V c.2450GNT No change Minor changes No change p.C491S c.1472GNC No change Disruption of ESE motifs Acceptor sites created p.I336L c.1006ANC No change Disruption of ESE motifs No change p.F305V c.913TNG Increased score for SRp55 Disruption of ESS motifs Donor gained (0.99) p.S511C c.1532CNG Decreased score for SC35 Disruption of ESS motifs No change p.S1311N c.3932GNA Changes on ss scores Disruption of ESS motifs Donor increased (0.50/0.63) p.L926F c.2778GNT No change Creation of ESS motifs Changes on ss scores p.A1225V c.3674CNT No change Disruption of ESE motif/creation of ESS motif Donor increased (0.72/0.99) p.F533L c.1597TNC No change Creation of ESE motifs/disruption of ESS motifs No change p.Q1209H c.3627ANC No change Minor changes No change c.2490+3ANG No change Minor changes No change c.2909-36TNC Decrease of donor ss Disruption of ESS motifs Acc increased (0.33/0.48)/donor increased (0.74/0.94) c.2909-10TNC Change for SRp55 best hit (3.97/5.16) Disruption of ESS motifs No change c.4137-21GNT No change Disruption of ESE and creation of ESS motifs Acc increased (0.86/0.96) c.1116+4ANT No change WT donor site disrupted Marginal changes on donor ss c.2988+30TNC No change Disruption of ESE motif/creation of ESS motif No change c.1680-27GNA No change Disruption of ESS motifs No change c.2620-24CNG No change Creation of ESE motifs Donor gained 0.96 c.2620-18delT No change New donor ss/changes on ESE and ESS motifs Acc increased (0.41/0.55) c.2658-8CNG Decreased score for acc site Minor changes Marginal changes on ss p.L1227L c.3681ANG No change Changes on ESE and ESS motifs No change p.R1158R c.3472CNA No change Creation of ESE motifs/creation of ESS motifs Marginal changes on ss p.D1275D c.3825TNC No change No change Donor increased (0.56/0.87) p.L346L c.1036CNT No change No change No change Abbreviations: ESE: exonic splicing enhancer, HSF: human splicing finder, ESS: exonic splicing silencer, WT: wild type, Mut: mutant, ss: splicing site. 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