Variant NM_000492.4:c.617T>G


Variant details:
Name NM_000492.4:c.617T>G
Protein name NP_000483.3:p.(Leu206Trp)
Genomic name (hg19) chr7:g.117175339T>G    UCSC    
#Exon/intron exon 6
Legacy Name L206W
Class disease-causing
Subclass varying clinical consequence
complex allele in 5.15% of patients associated with
  • c.1210-34_1210-6TG[9]T[9] : 100.00%
    • WT sequence GCACATTTCGTGTGGATCGCTCCTT T GCAAGTGGCACTCCTCATGGGGCTA
    Mutant sequence GCACATTTCGTGTGGATCGCTCCTT G GCAAGTGGCACTCCTCATGGGGCTA

    Other databases:
    dbSNP
    rs121908752



    Pathogenicity predictors:

    Functional studies:


    Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
    Clain et al, 2005 15776432 ✓ ✓ ✓
    Van Goor et al, 2014 23891399 ✓ ✓ ✓
    Sosnay et al, 2013 23974870 ✓ ✓


    « ✓ » 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
    IVA yesnono yes
    TEZ-IVA yes yesno yes
    ELX-TEZ-IVA yesnoyesno


    clinical and functional data are provided by Vertex


    No patient found in CFTR-NGS catalogue


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

    TOTAL NUMBER OF PATIENTS 136
    Asymptomatic compound heterozygote 3
    CF 28
    CFTR-RD71
    • Bronchiectasis  9
    • CBAVD  46
    • CRS-NP  1
    • Other  7
    • Pancreatitis  8
    Pending 2
    Pending (NBS) 29
    Pending non-CF 3




    Color code:   non disease-causing <   likely benign <   VUS <   likely pathogenic <   disease-causing

    Detailed genotypes:
    Phenotype Patient ID Variant status Additional variants
    CF 4899heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CF 2655heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CF 2827heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CF 3223heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CF 2253heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CF 5863heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CF 2016heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CF 2109heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CF 2197heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CF 6096heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CF 6202heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CF 4485heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CF 5622heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CF 3917heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CF 4390heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CF 4464heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CF 4479heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CF 38heterozygotevarying clinical consequence - Cis
    VUS3 - Trans
    CF 821heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CF 822heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CF 90heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CF 263heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CF 277heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CF 280heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CF 381heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CF 1693heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CF 5132heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CF 4782heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Other 4528heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Other 4676heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Other 5813heterozygoteCFTR-RD-causing- Undef
    varying clinical consequence- Undef
    Other 6357heterozygotevarying clinical consequence - Cis
    CFTR-RD-causing - Trans
    Other 4783heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Other 4800heterozygoteVUS3- Undef
    CF-causing- Undef
    VUS3- Undef
    varying clinical consequence- Undef
    Other 5184heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    VUS3- Undef
    VUS3- Undef
    CBAVD 5375heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CBAVD 4935heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CBAVD 4937heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CBAVD 2631heterozygotevarying clinical consequence - Cis
    VUS3- Undef
    CF-causing- Undef
    CBAVD 2817heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CBAVD 3353heterozygoteCFTR-RD-causing- Undef
    varying clinical consequence- Undef
    CBAVD 3374heterozygoteCFTR-RD-causing- Undef
    varying clinical consequence- Undef
    CBAVD 4877heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CBAVD 5459heterozygotevarying clinical consequence - Cis
    varying clinical consequence - Trans
    CBAVD 1930heterozygoteCF-causing- Undef
    VUS3- Undef
    varying clinical consequence- Undef
    CBAVD 2203heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CBAVD 3381heterozygoteCFTR-RD-causing- Undef
    varying clinical consequence- Undef
    CBAVD 3414heterozygotevarying clinical consequence- Undef
    varying clinical consequence- Undef
    CBAVD 4592heterozygotevarying clinical consequence - Cis
    CFTR-RD-causing - Trans
    CBAVD 4597heterozygoteCFTR-RD-causing- Undef
    varying clinical consequence- Undef
    CBAVD 6173heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CBAVD 5594heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CBAVD 548heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CBAVD 614heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CBAVD 643heterozygoteCFTR-RD-causing- Undef
    varying clinical consequence- Undef
    CBAVD 765heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CBAVD 834heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CBAVD 840heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CBAVD 857heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CBAVD 881heterozygoteCFTR-RD-causing- Undef
    varying clinical consequence- Undef
    CBAVD 912heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CBAVD 491heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CBAVD 490heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CBAVD 4679heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CBAVD 4837heterozygoteCFTR-RD-causing- Undef
    varying clinical consequence- Undef
    CBAVD 422heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CBAVD 434heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CBAVD 978heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CBAVD 1163heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CBAVD 1329heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CBAVD 1363heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CBAVD 1412heterozygoteVUS3- Undef
    varying clinical consequence- Undef
    CBAVD 1413heterozygoteCFTR-RD-causing- Undef
    varying clinical consequence- Undef
    CBAVD 1438heterozygoteCFTR-RD-causing- Undef
    varying clinical consequence- Undef
    CBAVD 1442heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CBAVD 1463heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CBAVD 1679heterozygotevarying clinical consequence- Undef
    varying clinical consequence- Undef
    CBAVD 1748heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CBAVD 5221heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    CBAVD 1052heterozygotevarying clinical consequence- Undef
    varying clinical consequence- Undef
    CBAVD 1056heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    Pending 4680heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Pending 6309heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Pending non-CF 4681heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Pending non-CF 4677heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Pending non-CF 4515heterozygotevarying clinical consequence - Cis
    varying clinical consequence - Trans
    Bronchiectasis 6405heterozygoteCFTR-RD-causing- Undef
    varying clinical consequence- Undef
    Bronchiectasis 2055heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    Bronchiectasis 4602heterozygoteCFTR-RD-causing- Undef
    varying clinical consequence- Undef
    Bronchiectasis 4488heterozygotevarying clinical consequence - Cis
    Bronchiectasis 850heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Bronchiectasis 4726heterozygotevarying clinical consequence - Cis
    CFTR-RD-causing- Undef
    Bronchiectasis 962heterozygoteVUS2 - Cis
    varying clinical consequence - Cis
    CF-causing - Trans
    Bronchiectasis 1096heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    Bronchiectasis 6344heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    Pending (NBS) 2964heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Pending (NBS) 3118heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    Pending (NBS) 4654heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Pending (NBS) 5443heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Pending (NBS) 6095heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    Pending (NBS) 6185heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Pending (NBS) 6001heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    Pending (NBS) 6100heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    Pending (NBS) 6008heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    Pending (NBS) 5342heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Pending (NBS) 3655heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Pending (NBS) 3676heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Pending (NBS) 3884heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Pending (NBS) 4228heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Pending (NBS) 4266heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    Pending (NBS) 4407heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Pending (NBS) 6011heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    Pending (NBS) 590heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Pending (NBS) 794heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Pending (NBS) 799heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Pending (NBS) 4821heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Pending (NBS) 1076heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Pending (NBS) 1180heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Pending (NBS) 1547heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Pending (NBS) 5190heterozygoteCF-causing- Undef
    VUS3- Undef
    VUS3- Undef
    varying clinical consequence- Undef
    Pending (NBS) 1064heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Pending (NBS) 5852heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Pending (NBS) 4769heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    Pending (NBS) 5046heterozygotevarying clinical consequence- Undef
    CF-causing- Undef
    Asymptomatic compound heterozygote 5376heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Asymptomatic compound heterozygote 6195heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    Asymptomatic compound heterozygote 5744heterozygoteVUS2- Undef
    varying clinical consequence- Undef
    Pancreatitis 2623heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    Pancreatitis 3259heterozygotevarying clinical consequence- Undef
    CF-causing- Undef
    Pancreatitis 5452heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    Pancreatitis 5864heterozygotevarying clinical consequence - Cis
    Pancreatitis 1960heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    Pancreatitis 2067heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    Pancreatitis 4270heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    Pancreatitis 1063heterozygotevarying clinical consequence - Cis
    CF-causing - Trans
    CRS-NP 6196heterozygoteCF-causing- Undef
    varying clinical consequence- Undef


    Color code:   non disease-causing <   likely benign <   VUS <   likely pathogenic <   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.



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