Variant NM_000492.4:c.3205G>A


Variant details:
Name NM_000492.4:c.3205G>A
Protein name NP_000483.3:p.(Gly1069Arg)
Genomic name (hg19) chr7:g.117251700G>A    UCSC    gnomAD
#Exon/intron exon 20
Legacy Name G1069R
Class disease-causing
Subclass CFTR-RD-causing
WT sequence AGGACTATGGACACTTCGTGCCTTC G GACGGCAGCCTTACTTTGAAACTCT
Mutant sequence AGGACTATGGACACTTCGTGCCTTC A GACGGCAGCCTTACTTTGAAACTCT


External sources:
dbSNP
rs200321110


Functional studies:


Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
Seibert et al, 1996 8662892 ✓ ✓
Sosnay et al, 2013 23974870 ✓ ✓
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
IVA yesnoyesno
TEZ-IVA yesnoyesno
ELX-TEZ-IVA yesnoyesno


clinical and functional data are provided by Vertex


Pathogenicity predictions:
AGVGD MAPP SIFT PPH2
C0 0.06734 0.3 0.772
VUS1 VUS2 VUS1 VUS4

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




No patient found in CFTR-NGS catalogue


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

TOTAL NUMBER OF PATIENTS 9
CFTR-RD9
  • Bronchiectasis  1
  • CBAVD  1
  • Pancreatitis  7



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
CBAVD 1355heterozygote
Pancreatitis 5024heterozygoteVUS3- Undef
Pancreatitis 5700heterozygoteCFTR-RD-causing- Undef
Pancreatitis 2091heterozygoteCF-causing- Undef
Pancreatitis 2441heterozygotevarying clinical consequence- Undef
Pancreatitis 3253heterozygoteCF-causing- Undef
Pancreatitis 5307heterozygotevarying clinical consequence- Undef
Pancreatitis 5339heterozygotevarying clinical consequence- Undef
VUS3- Undef
Bronchiectasis 2838heterozygoteCFTR-RD-causing- Undef
CFTR-RD-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.