Variant NM_000492.4:c.221G>A


Variant details:
Name NM_000492.4:c.221G>A
Protein name NP_000483.3:p.(Arg74Gln)
Genomic name (hg19) chr7:g.117149144G>A    UCSC    gnomAD
#Exon/intron exon 3
Legacy Name R74Q
Class VUS
Subclass VUS1
complex allele in 33.33% of patients associated with
  • c.890G>A - p.(Arg297Gln) : 100.00%
    • WT sequence AATCCTAAACTCATTAATGCCCTTC G GCGATGTTTTTTCTGGAGATTTATG
    Mutant sequence AATCCTAAACTCATTAATGCCCTTC A GCGATGTTTTTTCTGGAGATTTATG


    External sources:

    Not found    		dbSNP
    rs142540482


    Functional studies:


    Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
    LaRusch et al, 2014 25033378 ✓ ✓ ✓
    Bergougnoux et al, 2022 36567205 ✓ ✓ ✓ ✓ ✓


    « ✓ » 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 0.206 0.23 0.003
    VUS1 VUS1 VUS1 VUS1

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




    No patient found in CFTR-NGS catalogue


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

    TOTAL NUMBER OF PATIENTS 3
    CFTR-RD2
    • Pancreatitis  2
    Pending (NBS) 1



    Detailed genotypes:
    Phenotype Patient ID Variant status Additional variants
    Pancreatitis 3079heterozygoteVUS1- Undef
    Pancreatitis 4618heterozygoteVUS1- Undef
    Pending (NBS) 5312heterozygoteVUS1 - Cis
    CF-causing - 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.