CFTR S1235R - GET-Evidence

Curation:
Currentness:

CFTR S1235R

(CFTR Ser1235Arg)


Short summary

Reported to cause mild dysfunction of the cystic fibrosis gene, it may result in cystic fibrosis when combined with more severe variants.

Variant evidence
Computational 1

Polyphen 2 gives intermediate score (possibly damaging), other variants in this gene are associated with this disease

Functional -
Case/Control

Unclear how to find statistical significance from reports

See Weiss FU et al. 2005 (15987793).

Familial -
 
Clinical importance
Severity 3

cystic fibrosis, but this variant has a milder effect

Treatability 1
Penetrance 4

May require compound heterozygosity with a more severe mutation

 

Impact

Moderate clinical importance, Uncertain pathogenic

(The "moderate clinical importance, uncertain" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

recessive

Summary of published research, and additional commentary

 

Allele frequency

  • G @ chr7:117267812: 0.5% (57/10758) in EVS
  • G @ chr7:117055047: 0.8% (1/128) in GET-Evidence
  • Frequency shown in summary reports: 0.5% (57/10758)

Publications
 

Monaghan KG, Feldman GL, Barbarotto GM, Manji S, Desai TK, Snow K. Frequency and clinical significance of the S1235R mutation in the cystic fibrosis transmembrane conductance regulator gene: results from a collaborative study. Am J Med Genet. 2000 Dec 11;95(4):361-5. PubMed PMID: 11186891.

 

Weiss FU, Simon P, Bogdanova N, Mayerle J, Dworniczak B, Horst J, Lerch MM. Complete cystic fibrosis transmembrane conductance regulator gene sequencing in patients with idiopathic chronic pancreatitis and controls. Gut. 2005 Oct;54(10):1456-60. Epub 2005 Jun 29. PubMed PMID: 15987793; PubMed Central PMCID: PMC1774703.

The authors describe this mutation as “mild”.

Genomes
 

hu241DEA - CGI sample GS01175-DNA_D05 from PGP sample 1205491
het G @ chr7:117267812

 

hu342A08 - CGI sample GS01175-DNA_B05 from PGP sample 83494370
het G @ chr7:117267812

 

huAE6220 - CGI sample GS00253-DNA_H01_200_37
het G @ chr7:117267812

 

Other external references
 

    dbSNP
  • rs34911792
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    GeneTests
  • GeneTests records for the CFTR gene
    CFTR-Related Disorders
    CFTR-Related Hereditary Pancreatitis
    Hereditary Pancreatitis
    www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/CFTR
    PolyPhen-2
  • Score: 0.243 (possibly damaging)
    Web search results (122 hits -- see all)
  • CD00013
    ... (S1235R)]; a second allele tested negative for the S1235R mutation ... REGULATOR; CFTR. CYSTIC FIBROSIS; CF. Gene. CFTR. Chromosomal Location. 7q31.2. Allelic Variant 1. S1235R; CYSTIC ...
    ccr.coriell.org/Sections/Search/...?Ref=CD00013
  • CD00003
    ... 7 of the CFTR gene (1078delT) which results in a frameshift; a second allele tested negative for the S1235R ... region of the CFTR gene (polypyrimidine tract within the splice ...
    ccr.coriell.org/Sections/Search/...?Ref=CD00003&PgId=166
  • Genetically Characterized Positive Control Cell Lines Derived ...
    Cystic fibrosis (CFTR) S1235R; 7T/7T. DUK586982. Cystic fibrosis (CFTR) 1898 + 1G>A; 7T/7T ... DUK655842. Cystic fibrosis (CFTR) 1078delT; 7T/7T. DUK547322. Cystic fibrosis (CFTR) ...
    www.clinchem.org/cgi/content/full/51/11/2013/T2
  • Complete cystic fibrosis transmembrane conductance regulator ...
    Three of four severe CFTR mutations detected in patients were compound ... of severe genetic changes in the two CFTR alleles that reduces CFTR function to ...
    www.ncbi.nlm.nih.gov/pmc/articles/PMC1774703
  • Positive Controls are Now Positive Controls are Now Available ...
    CFTR. I148T WT. 7T/9T. V2. CD00013. Cystic Fibrosis. CFTR. S1235R. WT. 7T/7T ... Cystic Firbosis Assay, plus I148T and S1235R. The cell lines highlighted in light blue ...
    wwwn.cdc.gov/mlp/pdf/GeneticsQC/1104conference/LWillaims.pdf
  • Molecular characterization of the cystic fibrosis ...
    product of the CFTR transcript lacking exon 9 is devoid of cyclic ... S1235R and another CFTR mutation (DeltaF508del) was previ- ously described with a ...
    sigarra.up.pt/fmup/conteudos_service.conteudos_cont?...
  • Cystic Fibrosis Cell Lines
    R553X. 7T/9T. yes. B-lymphocyte. Coriell. GM07552. NA07552. yes. 1 lab. CFTR. G551D ... 1 lab. CFTR. S1235R. 7T/7T. yes. B-lymphocyte. Coriell. CD00013. CD00013. 6 ...
    wwwn.cdc.gov/dls/genetics/rmmaterials/pdf/cf.pdf
  • Isolated idiopathic chronic pancreatitis associated with a ...
    ... with a compound heterozygosity for two mutations of the CFTR gene. ... for mutations G542X and S1235R of the cystic fibrosis transmembrane regulator (CFTR) gene. The patient had ...
    www.ncbi.nlm.nih.gov/pubmed/14586256
  • Comprehensive and Rapid Genotyping of Mutations and ...
    ... of CFTR is needed for the diagnosis of patients with cystic fibrosis ... this strategy detected 87.9% of CFTR defects in congenital bilateral absence of ...
    jmd.amjpathol.org/cgi/content/full/9/5/582
  • Characterization of cystic fibrosis conductance transmembrane ...
    The CFTR gene is located on the long arm of chromosome 7 (region q31–q32) ... The CFTR protein has 1480 amino acid residues and is the main chloride channel ...
    humrep.oxfordjournals.org/cgi/content/full/19/11/2502

Other in silico analyses
 

  • NBLOSUM100 score = 3
  • GET-Evidence autoscore = 4

Edit history
 

Gene search

"GENE" or "GENE A123C":

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