Variant NM_000492.4:c.1327G>T


Variant details:
Name NM_000492.4:c.1327G>T
Protein name NP_000483.3:p.(Asp443Tyr)
Genomic name (hg19) chr7:g.117188812G>T    UCSC    gnomAD
#Exon/intron exon 10
Legacy Name D443Y
Class disease-causing
Subclass CFTR-RD-causing
complex allele in 73.97% of patients associated with
  • c.2002C>T - p.(Arg668Cys) : 98.15%
  • c.1727G>C - p.(Gly576Ala) : 100.00%
    • WT sequence ACTTCTTGGTACTCCTGTCCTGAAA G ATATTAATTTCAAGATAGAAAGAGG
    Mutant sequence ACTTCTTGGTACTCCTGTCCTGAAA T ATATTAATTTCAAGATAGAAAGAGG


    External sources:
    dbSNP
    rs147422190


    Functional studies:


    Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
    El-Seedy et al, 2012 22678879 ✓ ✓ ✓


    « ✓ » indicates the type of analysis performed and not the results


    Response to modulators:


    Modulator FDA approval EMA approval in vitro / ex vivo data clinical data
    IVAnononono
    TEZ-IVA yesnoyesno
    ELX-TEZ-IVA yesnoyesno


    clinical and functional data are provided by Vertex


    Pathogenicity predictions:
    AGVGD MAPP SIFT PPH2
    C0 0.01417 0.08 0.901
    VUS1 VUS4 VUS4 VUS5

    Color code:   non disease-causing <   VUS1 <   VUS2 <   VUS3 <   VUS4 <   VUS5 <   disease-causing




    No patient found in CFTR-NGS catalogue


    73 patients carrying this variant are reported in CFTR-France:

    TOTAL NUMBER OF PATIENTS 73
    Asymptomatic compound heterozygote 5
    CF 1
    CFTR-RD64
    • Bronchiectasis  2
    • CBAVD  52
    • CRS-NP  1
    • Other  6
    • Pancreatitis  3
    Pending 2
    Pending non-CF 1



    Detailed genotypes:
    Phenotype Patient ID Variant status Additional variants
    CBAVD 4612heterozygoteCF-causing- Undef
    CFTR-RD-causing- Undef
    CFTR-RD-causing- Undef
    CBAVD 3335heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing - Trans
    CBAVD 2989heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing - Trans
    CBAVD 4752heterozygoteCF-causing- Undef
    CFTR-RD-causing- Undef
    CFTR-RD-causing- Undef
    CBAVD 4646heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing - Trans
    CBAVD 2853heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing - Trans
    CBAVD 2824heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing- Undef
    CBAVD 2806heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing- Undef
    CBAVD 2756heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing- Undef
    CBAVD 2485heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing- Undef
    VUS1- Undef
    CBAVD 5882heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing - Trans
    CBAVD 5590heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing - Trans
    CBAVD 5764heterozygoteCF-causing- Undef
    CFTR-RD-causing- Undef
    CFTR-RD-causing- Undef
    CBAVD 4574heterozygoteCFTR-RD-causing- Undef
    CFTR-RD-causing- Undef
    CF-causing- Undef
    CBAVD 4571heterozygoteCF-causing- Undef
    CFTR-RD-causing- Undef
    CFTR-RD-causing- Undef
    CBAVD 4534heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing- Undef
    CBAVD 4331heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing - Trans
    CBAVD 4279heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing- Undef
    CBAVD 5947heterozygoteCF-causing- Undef
    CFTR-RD-causing- Undef
    CFTR-RD-causing- Undef
    CBAVD 5943heterozygoteCF-causing- Undef
    CFTR-RD-causing- Undef
    CFTR-RD-causing- Undef
    CBAVD 5610heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing - Trans
    CBAVD 5665heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CFTR-RD-causing - Trans
    CBAVD 5463heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing - Trans
    CBAVD 4683heterozygoteCF-causing- Undef
    CFTR-RD-causing- Undef
    CFTR-RD-causing- Undef
    CBAVD 659heterozygoteCFTR-RD-causing- Undef
    CFTR-RD-causing- Undef
    VUS3- Undef
    CBAVD 658heterozygoteCF-causing- Undef
    CFTR-RD-causing- Undef
    CFTR-RD-causing- Undef
    CBAVD 556heterozygoteCF-causing- Undef
    CFTR-RD-causing- Undef
    CFTR-RD-causing- Undef
    CBAVD 549heterozygoteCF-causing- Undef
    CFTR-RD-causing- Undef
    CFTR-RD-causing- Undef
    CBAVD 511heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    VUS4 - Trans
    CBAVD 508heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CFTR-RD-causing - Trans
    CBAVD 497heterozygoteCF-causing- Undef
    CFTR-RD-causing- Undef
    CFTR-RD-causing- Undef
    CBAVD 480heterozygoteCF-causing- Undef
    CFTR-RD-causing- Undef
    CFTR-RD-causing- Undef
    CBAVD 452heterozygoteCF-causing- Undef
    CFTR-RD-causing- Undef
    CFTR-RD-causing- Undef
    CBAVD 433heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing- Undef
    CBAVD 430heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing - Trans
    CBAVD 404heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    varying clinical consequence- Undef
    CBAVD 395heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing - Trans
    CBAVD 4735heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    varying clinical consequence - Trans
    CBAVD 4722heterozygoteCF-causing- Undef
    CFTR-RD-causing- Undef
    CFTR-RD-causing- Undef
    CBAVD 682heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing - Trans
    CBAVD 763heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing - Trans
    CBAVD 1745heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing- Undef
    CBAVD 1512heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing- Undef
    CBAVD 1510heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing- Undef
    CBAVD 1423heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing- Undef
    CBAVD 1381heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CBAVD 1365heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing- Undef
    CBAVD 1340heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing- Undef
    CBAVD 1335heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing- Undef
    CBAVD 1248heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing- Undef
    CBAVD 5181heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing - Trans
    VUS3- Undef
    CBAVD 900heterozygoteCF-causing- Undef
    CFTR-RD-causing- Undef
    CFTR-RD-causing- Undef
    Other 4570heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing - Trans
    Other 4809heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing- Undef
    Other 4278heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing - Trans
    VUS1- Undef
    Other 5083heterozygoteCFTR-RD-causing- Undef
    CFTR-RD-causing- Undef
    CF-causing- Undef
    Other 5814heterozygoteCF-causing- Undef
    CFTR-RD-causing- Undef
    CFTR-RD-causing- Undef
    Other 5264heterozygoteCFTR-RD-causing- Undef
    CFTR-RD-causing- Undef
    CF-causing- Undef
    Pending non-CF 4825heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    varying clinical consequence - Trans
    CF 5215heterozygoteVUS3- Undef
    CFTR-RD-causing- Undef
    CFTR-RD-causing- Undef
    Bronchiectasis 5669heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    VUS3 - Trans
    Bronchiectasis 5126heterozygoteCFTR-RD-causing- Undef
    CFTR-RD-causing- Undef
    Pancreatitis 2338heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    Pancreatitis 5740heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    Pancreatitis 4996homozygotec.1210-34_1210-6TG[11]T[5] - Trans
    c.1327G>T - p.(Asp443Tyr) - Trans
    c.1727G>C - p.(Gly576Ala) - Trans
    c.2002C>T - p.(Arg668Cys) - Trans
    Pending 2843heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing - Trans
    Pending 4304heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CRS-NP 3043heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing - Trans
    Asymptomatic compound heterozygote 3257heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing - Trans
    Asymptomatic compound heterozygote 4422heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    VUS4 - Trans
    Asymptomatic compound heterozygote 4260heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CFTR-RD-causing - Trans
    Asymptomatic compound heterozygote 5964heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    CF-causing - Trans
    Asymptomatic compound heterozygote 5602heterozygoteCFTR-RD-causing - Cis
    CFTR-RD-causing - Cis
    VUS3 - Trans


    Color code:   non disease-causing <   VUS1 <   VUS2 <   VUS3 <   VUS4 <   VUS5 <   disease-causing



                CFTR variants are clustered into five groups:
    • CF-causing: when in trans with another CF-causing mutation, will result in CF.
    • CFTR-RD causing: when in trans with a CF-causing mutation, will result in CFTR-related disorders (CFTR-RD) such as chronic pancreatitis, bronchiectasis, CRS-NP (chronic rhinosinusitis with or without nasal polyposis) or CBAVD (congenital absence of vas deferens), according to Bombieri C et al., 2011.
    • Varying clinical consequence: when in trans with another CF-causing mutation, can either result in CF or in a CFTR-RD.
    • Non disease-causing: when in trans with a CF-causing mutation, will not cause CF, nor CFTR-RD.
    • VUS (Variant of unknown clinical significance): unclassified because of insufficient data.