Variant NM_000492.4:c.772A>G


Variant details:
Name NM_000492.4:c.772A>G
Protein name NP_000483.3:p.(Arg258Gly)
Genomic name (hg19) chr7:g.117176630A>G    UCSC    gnomAD
#Exon/intron exon 7
Legacy Name R258G
Class disease-causing
Subclass CFTR-RD-causing
WT sequence TCAGAGAGCTGGGAAGATCAGTGAA A GACTTGTGATTACCTCAGAAATGAT
Mutant sequence TCAGAGAGCTGGGAAGATCAGTGAA G GACTTGTGATTACCTCAGAAATGAT


External sources:
dbSNP
rs191456345


Functional studies:


Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
Seibert et al, 1997 9305991 ✓ ✓ ✓


« ✓ » 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
C15 0.01104 0.02 0.891
VUS1 VUS4 VUS5 VUS4

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




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


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

TOTAL NUMBER OF PATIENTS 6
Asymptomatic compound heterozygote 1
CF 1
CFTR-RD4
  • Bronchiectasis  1
  • CBAVD  2
  • Pancreatitis  1



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
CBAVD 4682heterozygoteCF-causing- Undef
VUS1- Undef
CBAVD 4566heterozygoteCF-causing- Undef
CF 305heterozygoteCF-causing- Undef
Asymptomatic compound heterozygote 5513heterozygoteCF-causing - Trans
Pancreatitis 5892heterozygoteCF-causing- Undef
Bronchiectasis 4906heterozygoteCFTR-RD-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.