Variant NM_000492.4:c.349C>T


Variant details:
Name NM_000492.4:c.349C>T
Protein name NP_000483.3:p.(Arg117Cys)
Genomic name (hg19) chr7:g.117171028C>T    UCSC    gnomAD
#Exon/intron exon 4
Legacy Name R117C
Class disease-causing
Subclass varying clinical consequence
WT sequence CTATGACCCGGATAACAAGGAGGAA C GCTCTATCGCGATTTATCTAGGCAT
Mutant sequence CTATGACCCGGATAACAAGGAGGAA T GCTCTATCGCGATTTATCTAGGCAT


External sources:
dbSNP
rs77834169


Functional studies:


Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
Hammerle et al, 2001 11278813 ✓ ✓ ✓
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


Pathogenicity predictions:
AGVGD MAPP SIFT PPH2
C25 0.00073 0.01 1
VUS2 VUS5 VUS5 VUS5

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




No patient found in CFTR-NGS catalogue


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

TOTAL NUMBER OF PATIENTS 18
Asymptomatic compound heterozygote 2
CF 1
CFTR-RD12
  • Bronchiectasis  5
  • CBAVD  6
  • Other  1
Fetal bowel anomalies 1
Pending (NBS) 2



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
Asymptomatic compound heterozygote 540heterozygoteCF-causing - Trans
Asymptomatic compound heterozygote 4523heterozygoteCFTR-RD-causing - Trans
Fetal bowel anomalies 545heterozygote
CBAVD 3416heterozygoteCF-causing- Undef
CBAVD 3351heterozygoteCF-causing- Undef
CBAVD 4761heterozygoteCF-causing- Undef
CBAVD 1382heterozygoteCF-causing- Undef
CBAVD 1350heterozygoteCF-causing- Undef
CBAVD 546heterozygoteCF-causing - Trans
Bronchiectasis 5170heterozygoteCF-causing - Trans
Bronchiectasis 4623heterozygoteCF-causing- Undef
Bronchiectasis 5062heterozygoteCF-causing- Undef
Bronchiectasis 4848heterozygoteCF-causing - Trans
Bronchiectasis 1090heterozygoteCF-causing - Trans
VUS1 - Trans
CF 4865heterozygoteCF-causing- Undef
Pending (NBS) 3872heterozygoteCF-causing - Trans
Pending (NBS) 3771heterozygoteCF-causing - Trans
Other 4244heterozygoteCF-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.