ABCMdb

ABCC7 p.Tyr563*

ClinVar:

c.1687T>A , p.Tyr563Asn D , Pathogenic
c.1687T>G , p.Tyr563Asp ? , not provided

CF databases:

c.1687T>C , p.Tyr563His (CFTR1) D ,
c.1687T>A , p.Tyr563Asn (CFTR1) ? , This mutation is found in a single family with 2 PS patients, but the mutation in the other chromosome is unknown.
c.1687T>G , p.Tyr563Asp (CFTR1) ? , The Y563D mutation was detected on one African-American CF chromosome of 50 screened. It was not detected on any of 208 normal African-American chromosomes by ASO analysis. The patient is a 9 year old pancreatic insufficient male with mild lung disease.
c.1688A>G , p.Tyr563Cys (CFTR1) ? , The above mutation was detected by SSCP and identified by direct sequencing. The mutation destroys an AccI site which was used for confirmation.

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Publications
[hide] A haplotype framework for cystic fibrosis mutation... J Mol Diagn. 2006 Feb;8(1):119-27. Elahi E, Khodadad A, Kupershmidt I, Ghasemi F, Alinasab B, Naghizadeh R, Eason RG, Amini M, Esmaili M, Esmaeili Dooki MR, Sanati MH, Davis RW, Ronaghi M, Thorstenson YR
A haplotype framework for cystic fibrosis mutations in Iran.
J Mol Diagn. 2006 Feb;8(1):119-27., [PMID:16436643]

Abstract [show]
This is the first comprehensive profile of cystic fibrosis transmembrane conductance regulator (CFTR) mutations and their corresponding haplotypes in the Iranian population. All of the 27 CFTR exons of 60 unrelated Iranian CF patients were sequenced to identify disease-causing mutations. Eleven core haplotypes of CFTR were identified by genotyping six high-frequency simple nucleotide polymorphisms. The carrier frequency of 2.5 in 100 (1 in 40) was estimated from the frequency of heterozygous patients and suggests that contrary to popular belief, cystic fibrosis may be a common, under-diagnosed disease in Iran. A heterogeneous mutation spectrum was observed at the CFTR locus in 60 cystic fibrosis (CF) patients from Iran. Twenty putative disease-causing mutations were identified on 64 (53%) of the 120 chromosomes. The five most common Iranian mutations together represented 37% of the expected mutated alleles. The most frequent mutation, DeltaF508 (p.F508del), represented only 16% of the expected mutated alleles. The next most frequent mutations were c.1677del2 (p.515fs) at 7.5%, c.4041C>G (p.N1303K) at 5.6%, c.2183AA>G (p.684fs) at 5%, and c.3661A>T (p.K1177X) at 2.5%. Three of the five most frequent Iranian mutations are not included in a commonly used panel of CF mutations, underscoring the importance of identifying geographic-specific mutations in this population.

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Sentences [show]
No. Sentence Comment
111 of Patients Total alleles* Associated haplotype Global distributionHom Het Exon 1 c.134TϾC M1T 1 1 Rare Exon 3 c.386GϾA G85E 1 1 Global Exon 4 c.460GϾC D110H 1 1 H2 Europe Exon 7 c.1132CϾT R334W 1 1 H2 Global Exon 7 c.1145CϾT T338I 1 1 Europe Intron 9 c.1525-1GϾA Mis-splicing 1 1 H8 Pakistan Exon 10 c.1529CϾG S466X 1 2 H4 Germany Exon 10 c.1531CϾT L467F 1 1 Rare Exon 10 c.1649TϾC I506T 1 2 H8 Lebanon Exon 10 c.1652del3† ⌬F508 6 7 19 H5 Global Exon 10 c.1677delTA 515fs 4 1 9 H1 Europe Exon 11 c.1756GϾT G542X 1 1 H5 Global Exon 12 c.1821CϾA Y563X 2 2 Europe Exon 13 c.2183AAϾG 684fs 3 6 H3 Europe Exon 17a c.3170CϾT P1013L 1 1 Turkey Exon 19 c.3616CϾT R1162X 2 2 H2 Germany Exon 19 c.3661AϾT K1177X 1 1 3 H2 Bahrain Intron 20 c.4005ϩ1GϾA Mis-splicing 1 2 H2 Europe Exon 21 c.4041CϾG N1303K 3 1 7 H5 Global Exon 23 c.4363CϾT Q1412X 1 1 Rare *A total of 64 (53%) of the 120 expected alleles were observed. Login to comment
167 Haplotypes Observed in Iranian CF Patients and a European Control Group Haplotype c.876-33 (delTTGA) c.1001ϩ11 (C/T) c.1540 (A/G) c.3601-65 (C/A) c.4006-200 (G/A) c.4521 (G/A) Iranian CF patients (%) European controls (%) H0 7 C A C G A 1 2 H1 7 C G C G A 7 2 H2 7 C G C G G 25 39 H3 7 C A C G G 9 - H4 6 C A C G G 3 - H5 6 T A C G G 36 - H3, H4, H5 - - A C G G (48) 35 H6 7 C A A G G 3 0 H7 7 C G A G G 2 0 H8 7 C A C A G 3 0 H9 7 C A A A A 7 14 H10 7 C G A A A 5 9 Europe before it was introduced by migration, possibly from the Middle East.4,45 As for patients of European, Bashkortostanian, and Turkish descent, the vast majority (18 of 19) of the ⌬F508 alleles were associated with allele 6 of the TTGA repeat in intron 6b.9,46,47 All ⌬F508 mutations were found on the same SNP haplotype background, consistent with a report that ⌬F508 had extensive allele sharing of STR haplotypes in a French population48 and its complete linkage with a single variant of the intron 9 splice site polymorphism.49 All other CFTR mutations found on more than one chromosome, except p.Y563X, could be assigned to a single haplotype (Table 1). Login to comment

[hide] Variation in a repeat sequence determines whether ... Am J Hum Genet. 2004 Jan;74(1):176-9. Epub 2003 Dec 18. Groman JD, Hefferon TW, Casals T, Bassas L, Estivill X, Des Georges M, Guittard C, Koudova M, Fallin MD, Nemeth K, Fekete G, Kadasi L, Friedman K, Schwarz M, Bombieri C, Pignatti PF, Kanavakis E, Tzetis M, Schwartz M, Novelli G, D'Apice MR, Sobczynska-Tomaszewska A, Bal J, Stuhrmann M, Macek M Jr, Claustres M, Cutting GR
Variation in a repeat sequence determines whether a common variant of the cystic fibrosis transmembrane conductance regulator gene is pathogenic or benign.
Am J Hum Genet. 2004 Jan;74(1):176-9. Epub 2003 Dec 18., [PMID:14685937]

Abstract [show]
An abbreviated tract of five thymidines (5T) in intron 8 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene is found in approximately 10% of individuals in the general population. When found in trans with a severe CFTR mutation, 5T can result in male infertility, nonclassic cystic fibrosis, or a normal phenotype. To test whether the number of TG repeats adjacent to 5T influences disease penetrance, we determined TG repeat number in 98 patients with male infertility due to congenital absence of the vas deferens, 9 patients with nonclassic CF, and 27 unaffected individuals (fertile men). Each of the individuals in this study had a severe CFTR mutation on one CFTR gene and 5T on the other. Of the unaffected individuals, 78% (21 of 27) had 5T adjacent to 11 TG repeats, compared with 9% (10 of 107) of affected individuals. Conversely, 91% (97 of 107) of affected individuals had 12 or 13 TG repeats, versus only 22% (6 of 27) of unaffected individuals (P<.00001). Those individuals with 5T adjacent to either 12 or 13 TG repeats were substantially more likely to exhibit an abnormal phenotype than those with 5T adjacent to 11 TG repeats (odds ratio 34.0, 95% CI 11.1-103.7, P<.00001). Thus, determination of TG repeat number will allow for more accurate prediction of benign versus pathogenic 5T alleles.

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No. Sentence Comment
37 Each of the 98 patients with CBAVD had 5T with one of the following mutations: DF508 (78), G542X (6), N1303K (3), 711af9;1GrT (2), R1066C (2), R1162X (2), R764X (1), Y563X (1), H609R (1), L206W (1), or R334W (1). Login to comment
38 5T was confirmed by use of pedigree analysis to be in trans with R764X, Y563X, and H609X and was inferred as in trans for the remaining mutations, since these mutations have never been found to be in linkage disequilibrium with 5T in previous population sampling. Login to comment