Variant NM_000492.4:c.3485G>T


Variant details:
Name NM_000492.4:c.3485G>T
Protein name NP_000483.3:p.(Arg1162Leu)
Genomic name (hg19) chr7:g.117267592G>T    UCSC    gnomAD
#Exon/intron exon 22
Legacy Name 3617G/T
Class disease-causing
Subclass CFTR-RD-causing
WT sequence TTATTTCAGATGCGATCTGTGAGCC G AGTCTTTAAGTTCATTGACATGCCA
Mutant sequence TTATTTCAGATGCGATCTGTGAGCC T AGTCTTTAAGTTCATTGACATGCCA


External sources:
dbSNP
rs1800120


Functional studies:


Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
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 yesnoyesno
TEZ-IVA yesnoyesno
ELX-TEZ-IVA yesnoyesno


clinical and functional data are provided by Vertex


Pathogenicity predictions:
AGVGD MAPP SIFT PPH2
C0 0.05801 0.14 0.978
VUS1 VUS2 VUS2 VUS5

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




2 individuals carrying this variant are reported in CFTR-NGS catalogue


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

TOTAL NUMBER OF PATIENTS 13
Asymptomatic compound heterozygote 4
CFTR-RD7
  • Bronchiectasis  2
  • CBAVD  1
  • Other  2
  • Pancreatitis  2
Pending 1
Pending (NBS) 1



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
Pending 243heterozygote
CBAVD 963heterozygoteCFTR-RD-causing- Undef
Asymptomatic compound heterozygote 5004heterozygoteCF-causing - Trans
Asymptomatic compound heterozygote 2928heterozygoteVUS1 - Trans
Asymptomatic compound heterozygote 1935heterozygoteCF-causing- Undef
Asymptomatic compound heterozygote 5848heterozygote
Pancreatitis 2351heterozygoteVUS3- Undef
Pancreatitis 4255heterozygote
Bronchiectasis 2420heterozygoteCF-causing- Undef
Bronchiectasis 2406heterozygoteCFTR-RD-causing- Undef
Other 3047heterozygoteCF-causing - Trans
Other 2434heterozygoteCF-causing- Undef
Pending (NBS) 2520heterozygoteCF-causing- Undef


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.