ABCC7 p.Phe1016Ser
| ClinVar: |
c.3047T>C
,
p.Phe1016Ser
?
, not provided
|
| CF databases: |
c.3047T>C
,
p.Phe1016Ser
(CFTR1)
?
, This mutation was identified in a Hispanic female (three year old) patient who carries another novel mutation, the 1285_1288dupTA on the other chromosome.
|
| Predicted by SNAP2: | A: N (66%), C: N (57%), D: D (85%), E: D (80%), G: D (75%), H: D (80%), I: N (78%), K: D (85%), L: N (82%), M: N (82%), N: D (80%), P: D (85%), Q: D (80%), R: D (80%), S: D (66%), T: D (63%), V: N (72%), W: D (80%), Y: D (75%), |
| Predicted by PROVEAN: | A: N, C: N, D: D, E: D, G: D, H: D, I: N, K: D, L: N, M: N, N: D, P: D, Q: D, R: D, S: N, T: N, V: N, W: N, Y: N, |
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[hide] Identification of novel and rare mutations in Cali... Hum Mutat. 2004 Oct;24(4):353. Alper OM, Wong LJ, Young S, Pearl M, Graham S, Sherwin J, Nussbaum E, Nielson D, Platzker A, Davies Z, Lieberthal A, Chin T, Shay G, Hardy K, Kharrazi M
Identification of novel and rare mutations in California Hispanic and African American cystic fibrosis patients.
Hum Mutat. 2004 Oct;24(4):353., [PMID:15365999]
Abstract [show]
In ethnic heterogeneous California, complete genetic information is currently lacking to build solid population-based cystic fibrosis (CF) screening programs because a large proportion of mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR/ABCC7) are still unknown, especially in non-Caucasian patients. A total of 402 [46 African American+356 Hispanic] Hispanic and African American patients from California CF patient registry were included in this study. Patients with at least one unidentified mutant allele were asked to donate blood samples for further analysis, first by Genzyme Genetics for a panel of 87 known mutations, followed by temporal temperature gradient gel electrophoresis (TTGE) scanning of the entire coding exons of CFTR gene. A total of eight novel mutations; one missense mutation, one splice-site mutation and six frame-shift mutations were identified. In addition to the eight novel mutations, 20 [corrected] distinct rare mutations that are not in the current available commercial mutation panels were identified by TTGE. The overall detection rate was raised to 95.7% for African American and 94.5% for Hispanic. The discovery of recurrent rare and novel mutations improves the diagnosis and care of persons with CF and improves our ability to adequately and equitably provide screening and genetic counseling services to non-Caucasians.
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No. Sentence Comment
80 3179 T>C (c.3047T>C, p.Phe1016Ser): The missense mutation p. Phe1016Ser is caused by the transition thymine to cytosine at nucleotide position 3179 in exon 17a of the CFTR gene.
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ABCC7 p.Phe1016Ser 15365999:80:23
status: NEWX
ABCC7 p.Phe1016Ser 15365999:80:61
status: NEW63 A total of eight novel mutations: one missense mutation 3179T>C, (c.3047T>C, p.Phe1016Ser), six frame-shift mutations: 124_146del23bp (c.-9_14del23), 360_365insT (c.233dupT, p.Phe77fs), 379_381insT (c.248dupT, p.Phe83fs), 1285_1288dupTA (c.1153_1154dupTA, p.Tyr385fs), 2289_2295del7insGT (c.2157_2163del7insGT, p.Leu719fs), and 3960_3961delA (c.3828delA, p.Ser1276fs), and one splice-site mutation, were discovered (Table 1A).
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ABCC7 p.Phe1016Ser 15365999:63:79
status: NEW72 Novel Mutations Nucleotide change-position Traditional nomenclature Approved nomenclature Protein Mutation/ Effect Exon/ Intron Number of chromosomes 124_146del23bp c.- 9_14del23 No translation initiation 5`UTR 1 296+2T>A c.164+2T>A splice mutation/ truncation int 2 2 (sib) 360_365 insT c.233dupT p.Phe77fs frameshift/ truncation 3 1 379_381 insT c.248dupT p.Phe83fs frameshift/ truncation 3 1 1285_1288dupTA c.1153_1154dupTA p.Tyr385fs frameshift/ truncation 8 6 (1 homo) 2289_2295 del 7bp insGT c.2157_2163del7insGT p.Leu719fs frameshift/ truncation 13 1 3179 T>C c.3047T>C p.Phe1016Ser missense mutation 17a 1 3960_3961 del A c.3828delA p.Ser1276fs frameshift/ truncation 20 1 Mutations identified in African Americans are in bold. Table 1B.
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ABCC7 p.Phe1016Ser 15365999:72:579
status: NEW82 p.Phe1016Ser was found in a three year-old Hispanic female patient (# 1, Table 2A) who carries another novel mutation, the 1285_1288dupTA on the other chromosome.
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ABCC7 p.Phe1016Ser 15365999:82:2
status: NEW135 Clinical Presentations of Five Cystic Fibrosis Cases with Novel 1288insTA Mutation # 1 # 2 # 3 # 4 # 5 Agea /age at diagnosis 3y / 4m 19m / 4m 5y / 8m 6y / 6m 4y / 2m Mutation 1 p.Phe1016Ser 406-1G>A p.Ser492Phe 3876delA 1285_1288dupTA Mutation 2 1285_1288dupTA 1285_1288dupTA 1285_1288dupTA 1285_1288dupTA 1285_1288dupTA Sweat Cl-(mEq/L) b 92 84 97 87 91 FVC (%)a n/a n/a 100 72 n/a FEV1 (%)a n/a n/a 88 62 n/a Infection / Complication Probable haemophilus species, M. Catarrhalis S. aureus, P.aeruginosa none S. aureus, S. marcencens, haemophilus species, respiratory syncytial virus infection (RSV) P. aeruginosa, A. terreus, ABPA Height (cm) a percentile) 93cm (10%) 76cm (5%) 115cm (75%) 116.8cm (10-25%) 102cm (50%) Weight (kg) a percentile) 13.8kg (10-25%) 9kg (<5%) 23kg (95%) 19.9kg (10-25%) 16kg (50%) IRT c (ug/dL) n/a n/a n/a 198,2 n/a Meconium ileus no no no no no Pancreatic function PI PI PI PI PI Enzyme Creon 5 (2/meal,1/snack) Ultrase MT 10 (2/meal, 1/snack) Ultrase MT 12 (3/meal, 1/snack) Creon 10 (5/meal,4/snack) Ultrase (2/meal, 1/snack); Viokase (1/2 tsp/ nocturnal G-tube feeding) Ethnicity Hispanic Hispanic Hispanic Hispanic Hispanic National Origin Mexico Mexico and Native American Mexico Mother - Mexico Father - SanSalvador Mexico Sex F F M M M Family History no known family history no known family history no known family history no known family history Parents are 1st cousins Clinical presentation prior to diagnosis severe FTT, pneumonia, GERD FTT, recurrent respiratory tract infections frequent cough, respiratory tract infections recurrent pneumonia FTT Novel mutations indicated in bold. a at blood draw, b age at sweat Cl- is the same as age at diagnosis, c IRT (immunoreactive trypsin) measured from archived Guthrie cards, if available. ABPA: allergic bronchopulmonary aspergillosis, F: female, FEV: Forced expiratory volume, FVC: Forced vital capacity, FTT: Failure to thrive, GERD: gastroesophageal reflux disease, G-tube: gastrointestinal tube, M: male; m: months, MI: meconium ileus, n/a: not available, PI: Pancreatic insufficient, PS: pancreatic sufficient, y: years.
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ABCC7 p.Phe1016Ser 15365999:135:180
status: NEW140 Except for the p.Phe1016Ser missense mutation, all of the novel mutations are frame shift or splice-site mutations that produce truncated CFTR proteins, expected to be deleterious.
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ABCC7 p.Phe1016Ser 15365999:140:17
status: NEW[hide] Detection of CFTR mutations using temporal tempera... Electrophoresis. 2004 Aug;25(15):2593-601. Wong LJ, Alper OM
Detection of CFTR mutations using temporal temperature gradient gel electrophoresis.
Electrophoresis. 2004 Aug;25(15):2593-601., [PMID:15300780]
Abstract [show]
Cystic fibrosis (CF), caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, is one of the most common autosomal recessive diseases with variable incidences and mutation spectra among different ethnic groups. Current commercially available mutation panels designed for the analysis of known recurrent mutations have a detection rate between 38 to 95%, depending upon the ethnic background of the patient. We describe the application of a novel mutation detection method, temporal temperature gradient gel electrophoresis (TTGE), to the study of the molecular genetics of Hispanic CF patients. TTGE effectively identified numerous rare and novel mutations and polymorphisms. One interesting observation is that the majority of the novel mutations are splice site, frame shift, or nonsense mutations that cause severe clinical phenotypes. Our data demonstrate that screening of the 27 exons and intron/exon junctions of the CFTR gene by TTGE greatly improves the molecular diagnosis of Hispanic CF patients.
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No. Sentence Comment
133 Identification of rare and novel mutations and polymorphisms Base substitution Mutation Exon or intron Homozygote or heterozygote Polymorphism or mutation # Alleles identified 1 c.124_146del23bp Frameshift 1 Heterozygote Mutation 1 2 c.296+2T>A Splice Int 2 Heterozygote Mutation 1 3 c.296+28A/G Int 2 Homozygote Polymorphism 2 4 c.355CT p.R75X 3 Heterozygote Mutation 2 5 c.360_365insT Frameshift 3 Heterozygote Mutation 1 6 c.379_381insT Frameshift 3 Heterozygote Mutation 1 7 c.406-1G>A Splice Int 4 Heterozygote Mutation 2 8 c.424C.T p.Q98X 4 Heterozygote Mutation 1 9 c.425A.G p.Q98R 4 Heterozygote Mutation 3 10 c.586A.G p.M152V 4 Homozygote Mutation 2 11 c.663delT Frameshift 5 Heterozygote Mutation 3 12 c.667C>A p.Q179K 5 Heterozygote Mutation, 1 13 c.745C.T p.P205S 6a Heterozygote Mutation 5 14 c.875140A/G 6a Heterozygote Polymorphism 11 15 c.935delA Frameshift 6b Heterozygote Mutation 2 16 c.124811G.A Splice Int 7 Heterozygote Mutation 2 17 c.1285ins TA Frameshift 8 Heterozygote Mutation 4 Homozygote Mutation 2 18 c.1342+196C/T Int 8 Heterozygote Polymorphism 4 Homozygote 2 19 c.1461insAGAT Frameshift 9 Heterozygote Mutation 1 20 c.1525-61A/G 10 Heterozygote Polymorphism 22 21 c.1529C.A/G p.S466X 10 Heterozygote Mutation 1 22 c.1607C.T p.S492F 10 Heterozygote Mutation 3 23 c.1814C.T p.A561E 12 Heterozygote Mutation 1 24 c.189813A.G Splice Int 12 Heterozygote Mutation 1 25 c.18981152T/A Int 12 Heterozygote Polymorphism 5 26 c.1924del 7bp Frameshift 13 Heterozygote Mutation 1 27 c.1949del84 Frameshift 13 Heterozygote Mutation 1 28 c.2055del9toA Frameshift 13 Homozygote Mutation 2 29 c.2105_2117 Frameshift 13 Heterozygote Mutation 4 del13insAGAAA 30 c.2108delA Frameshift 13 Heterozygote Mutation 1 31 c.2184insA Frameshift 13 Heterozygote Mutation 2 32 c.2184delA Frameshift 13 Heterozygote Mutation 1 33 c.2289_2295 Frameshift 13 Heterozygote Mutation 1 del7insGT 34 c.2694T.G p.T854T 14a Heterozygote Polymorphism 10 35 c.2752+12G/C Int 14a Heterozygote Polymorphism 2 36 c.2800C.T p.Q890X 15 Homozygote Mutation 2 37 c.3171delC Frameshift 17a Heterozygote Mutation 1 38 c.3179T>C p.F1016S 17a Heterozygote Mutation 1 39 c.3199del 6bp Frameshift 17a Heterozygote Mutation 1 40 c.3212T.C p.I1027T 17a Heterozygote Mutation 1 41 c.3272-26A.G Splice Int17a Heterozygote Mutation 4 42 c.3271delGG Frameshift 17a Heterozygote Mutation 1 43 c.3313G.C p.G1061R 17b Heterozygote Mutation 1 44 c.3328C.T p.R1066C 17b Heterozygote Mutation 2 45 c.3362T.C p.L1077P 17b Heterozygote Mutation 1 46 c.3431A.C p.Q1100P 17b Heterozygote Mutation 1 47 c.3500-2A>T Splice Int 17b Heterozygote Mutation 1 48 c.3743G.A p.W1204X 19 Heterozygote Mutation 1 Homozygote Mutation 2 49 c.3601-65C/A Int 19 Heterozygote Polymorphism 14 50 c.3863G.A p.G1244E 20 Heterozygote Mutation 3 Table 3.
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ABCC7 p.Phe1016Ser 15300780:133:2112
status: NEW[hide] Multiplex ligation-dependent probe amplification i... J Mol Diagn. 2008 Jul;10(4):368-75. Epub 2008 Jun 13. Schrijver I, Rappahahn K, Pique L, Kharrazi M, Wong LJ
Multiplex ligation-dependent probe amplification identification of whole exon and single nucleotide deletions in the CFTR gene of Hispanic individuals with cystic fibrosis.
J Mol Diagn. 2008 Jul;10(4):368-75. Epub 2008 Jun 13., [PMID:18556774]
Abstract [show]
A disparity between Caucasian and Hispanic mutation detection for cystic fibrosis continues to exist, although the carrier frequency is only moderately lower in Hispanics. We aimed to identify exonic rearrangements that remained undetected by conventional methods. In seven of 32 cystic fibrosis-affected self-identified Hispanics for whom only one or no mutations were identified by extensive molecular testing, exon deletions appeared to be present with a multiplex ligation-dependent probe amplification (MLPA) assay. Two recurrent deletions (of exons 2-3 and exons 22-23) were identified in one and three patients, respectively (12.5%, 11.1% of unidentified alleles). Two apparently novel deletions (exons 6b and 20) were identified in three additional patients. Subsequent sequencing to characterize deletion breakpoints, however, identified single nucleotide deletions at the probe binding sites close to the ligation point. All resulted in false positive MLPA deletion signals. Interestingly, these mutations were not common in Caucasians, and one (935delA) was common in U.S. Hispanics. On examination of all probe binding sites, we identified a total of 76 reported mutations and five silent variants that immediately surrounded the MLPA ligation sites, with 22 occurring in non-Caucasians. These mutations are not all rare. Thus, apparent exon deletions by MLPA may indicate the presence of both large deletions and point mutations, with important implications for pan-ethnic MLPA testing in cystic fibrosis and other genetic conditions.
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No. Sentence Comment
112 Mutations under MLPA Ligation Sites Exon Probe length (nt) Ligation site sequence Mutations in area of ligation site sequence* 1,5Ј UTR 154 5Ј-GAGCAAAT-TTGGGGCC-3Ј N/A 1,5Ј UTR 238 5Ј-AAAGGGTT-GAGCGGCA-3Ј 2 198 5Ј-TTGGTATA-TGTCTGAC-3Ј (5) 3 136 5Ј-CTGCTAGT-GTTGCCAA-3Ј (3) 3 220 5Ј-TTCAAAGA-AAAATCCT-3Ј 4 247 5Ј-AGAATCAT-AGCTTCCT-3Ј 444delA, African; 451del8, Chinese; (6) 5 346 5Ј-AAATAAGT-ATTGGACA-3Ј Q179K, Hispanic (7) 6a 274 5Ј-GAGTTGTT-ACAGGCGT-3Ј L218X, Pakistani (4) 6b 301 5Ј-ATTTTCAA-TCATTTCT-3Ј 935delA, Hispanic; 936delTA, Hispanic (3) 7 337 5Ј-ACTTCAAT-AGCTCAGC-3Ј S307N, Turkish (9) 8, IVS 8 364 5Ј-TTTCTAGA-TTAAGAAG-3Ј N/A 9, IVS 8 391 5Ј-TCCATCAC-ACTGGTAG-3Ј N/A 10 463 5Ј-TCCACTGT-GCTTAATT-3Ј H484Y, Hispanic; S485C, Chinese-Caucasian (5) 11 418 5Ј-CAGAGAAA-GACAATAT-3Ј K536X, Iranian; 1742delAC, Japanese (5) 12, IVS 12 292 5Ј-TGCATTTT-ACCTCTTG-3Ј N/A 13 142 5Ј-CAGATTCT-GAGCAGGG-3Ј (1) 14a 160 5Ј-GTATGTGT-TCCATGTA-3Ј (3) 14b 178 5Ј-CTGCTTCT-TTGGTTGT-3Ј 2766del8, Tunisian (1) 15 204 5Ј-GCTTGCTA-TGGGATTC-3Ј (1) 16, IVS 16 229 5Ј-GATGTAAT-AGCTGTCT-3Ј N/A 17a 256 5Ј-TGCAACAA-AGATGTAG-3Ј 3171delC, Hispanic; 3173delAC, Turkish; F1016S, Hispanic (5) 17b 283 5Ј-CAGTATGT-AAATTCAG-3Ј H1085R, Japanese (4) 18 310 5Ј-CCATGAAT-ATCATGAG-3Ј M1137R, Hispanic (6) 19 353 5Ј-TCTGTGTA-TTTTGCTG-3Ј 3791delC, African-American (2) 20 382 5Ј-CTTGGGAT-TCAATAAC-3Ј 3960delA, Hispanic (2) 21 409 5Ј-TGCAACTT-TCCATATT-3Ј W1316X, African-American (2) 22 436 5Ј-GAACAGTT-TCCTGGGA-3Ј No mutations 23 148 5Ј-CCAGCATT-GCTTCTAT-3Ј M1407T, Turkish; E1409K, Hispanic (2) 24 190 5Ј-ATCCAGAA-ACTGCTGA-3Ј No mutations 24 172 5Ј-CTCCTCTT-TCAGAGCA-3Ј UTR, untranslated region; IVS, intervening sequence; N/A, not applicable, probes not in coding region; No mutations, no reported mutations are present in the area of the ligation site sequence, regardless of ethnicity.
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ABCC7 p.Phe1016Ser 18556774:112:1410
status: NEW