Variant NM_000492.4:c.3197G>A


Variant details:
Name NM_000492.4:c.3197G>A
Protein name NP_000483.3:p.(Arg1066His)
Genomic name (hg19) chr7:g.117251692G>A    UCSC    gnomAD
#Exon/intron exon 20
Legacy Name R1066H
Class disease-causing
Subclass CF-causing
WT sequence AGCTTAAAAGGACTATGGACACTTC G TGCCTTCGGACGGCAGCCTTACTTT
Mutant sequence AGCTTAAAAGGACTATGGACACTTC A TGCCTTCGGACGGCAGCCTTACTTT


External sources:
dbSNP
rs121909019


Functional studies:


Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
Seibert et al, 1996 8662892 ✓ ✓
Cotten et al, 1996 8702904 ✓ ✓
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
IVAnononono
TEZ-IVA yesnoyesno
ELX-TEZ-IVA yesnoyesno


clinical and functional data are provided by Vertex


Pathogenicity predictions:
AGVGD MAPP SIFT PPH2
C0 0.03537 0.02 0.998
VUS1 VUS4 VUS5 VUS5

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




No patient found in CFTR-NGS catalogue


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

TOTAL NUMBER OF PATIENTS 5
CF 5



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
CF 5023heterozygoteCF-causing- Undef
CF 1948heterozygoteVUS1 - Cis
CF-causing - Trans
CF 3115heterozygoteCF-causing - Trans
CF 3536heterozygoteCF-causing- Undef
CF 3766heterozygotevarying clinical consequence- 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.