ABCC7 p.Met1Val
| Admin's notes: | Class II-III (maturation defect, gating defect) Veit et al. |
| ClinVar: |
c.3G>T
,
p.Met1Ile
?
, not provided
c.3G>A , p.Met1Ile ? , not provided c.2T>A , p.Met1Lys ? , not provided c.1A>G , p.Met1Val D , Pathogenic |
| CF databases: |
c.1A>G
,
p.Met1Val
D
, CF-causing ; CFTR1: We believe that this is disease causing because: (i) In eukaryotes, the triplet AUG provides the sole translation initiation codon, (it is only in bacteria that the GUG triplet is sometimes used). (ii) We have not identified any other mutations in this CF chromosome, having sequenced 1-5, 6a, 6b, 7-12, 14a, 14b, 17b and 19-24. (iii) We have failed to identify this substitution on 45 normal chromosomes and over 50 [delta]F508 CF chromosomes. The mutation destroys an NlaIII site and creates a BsqI site. The mutation accounts for 0.3% (1/369) of our total CF chromosomes.
c.3G>A , p.Met1Ile (CFTR1) D , This mutation lies on exon 1 in the initiation codon and at nucleotide position 135 G->A. Following the approved nomenclature, we have called this mutation M1I. M1I was detected by SSCP analysis followed by direct sequencing and has been confirmed by an N1a III restriction digest. This patient is aknown affected cystic fibrosis sufferer and carries the [delta]F508 mutation on the other chromosome. Unfortunately we do not have nay other clinical data on this patient at the present time. c.2T>A , p.Met1Lys (CFTR1) D , This mutation was detected by DGGE. It destroys a NlaIII restriction site. It has been found in one CF patient from Southern France. c.3G>T , p.Met1Ile (CFTR1) D , M1I was previously reported by Axton and Brock (NL#61), but with a GA nucleotide change. This mutation was found in one nine-year old male, PI, with mild pulmonary disease. The other allele is [delta]F508. S10R, a change of a neutral amino acid for a basic one, was found in one 4 year old boy, PI, with moderate pulmonary disease. This mutation was found once on 174 non-[delta]F508 chromosomes. c.1A>C , p.Met1Leu (CFTR1) ? , c.2T>C , p.Met1Thr (CFTR1) ? , This mutation is supposed to prevent initiation of the translation. It abolishes a NlaIII restriction site. It was found in a CF girl with a mild PS form, nasal polyposis and positive sweat tests. She carries R334W on the other CF chromosome. c.2T>G , p.Met1Arg (CFTR1) ? , |
| Predicted by SNAP2: | A: D (66%), C: N (53%), D: D (80%), E: D (75%), F: D (59%), G: D (75%), H: D (66%), I: N (61%), K: D (71%), L: N (87%), N: D (71%), P: D (80%), Q: D (59%), R: D (71%), S: D (66%), T: D (66%), V: N (93%), W: D (71%), Y: D (63%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, N: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: N, Y: N, |
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Comments [show]
[hide] A Genotypic-Oriented View of CFTR Genetics Highlig... Mol Med. 2015 Apr 21;21:257-75. doi: 10.2119/molmed.2014.00229. Lucarelli M, Bruno SM, Pierandrei S, Ferraguti G, Stamato A, Narzi F, Amato A, Cimino G, Bertasi S, Quattrucci S, Strom R
A Genotypic-Oriented View of CFTR Genetics Highlights Specific Mutational Patterns Underlying Clinical Macrocategories of Cystic Fibrosis.
Mol Med. 2015 Apr 21;21:257-75. doi: 10.2119/molmed.2014.00229., [PMID:25910067]
Abstract [show]
Cystic fibrosis (CF) is a monogenic disease caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The genotype-phenotype relationship in this disease is still unclear, and diagnostic, prognostic and therapeutic challenges persist. We enrolled 610 patients with different forms of CF and studied them from a clinical, biochemical, microbiological and genetic point of view. Overall, there were 125 different mutated alleles (11 with novel mutations and 10 with complex mutations) and 225 genotypes. A strong correlation between mutational patterns at the genotypic level and phenotypic macrocategories emerged. This specificity appears to largely depend on rare and individual mutations, as well as on the varying prevalence of common alleles in different clinical macrocategories. However, 19 genotypes appeared to underlie different clinical forms of the disease. The dissection of the pathway from the CFTR mutated genotype to the clinical phenotype allowed to identify at least two components of the variability usually found in the genotype-phenotype relationship. One component seems to depend on the genetic variation of CFTR, the other component on the cumulative effect of variations in other genes and cellular pathways independent from CFTR. The experimental dissection of the overall biological CFTR pathway appears to be a powerful approach for a better comprehension of the genotype-phenotype relationship. However, a change from an allele-oriented to a genotypic-oriented view of CFTR genetics is mandatory, as well as a better assessment of sources of variability within the CFTR pathway.
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No. Sentence Comment
362 Allele legacy name Allele HGVS name Clinical classification CFTR2 M1V c.1A>G CF-PI CF-causing p.Met1Val P5L c.14C>T CF-PS,CFTR-RD nd p.Pro5Leu ex2,3del c.54-5940_273+10250del21080 CF-PI CF-causing ex2del c.54-1161_164+1603del2875 CF-PI nd W19X(TAG) c.56G>A CF-PI nd p.Trp19* [L24F;296+2T>G] c.
X
ABCC7 p.Met1Val 25910067:362:96
status: NEW
admin on 2016-08-19 15:16:22