Variant NM_000492.4:c.1054C>T


Variant details:
Name NM_000492.4:c.1054C>T
Protein name NP_000483.3:p.(Arg352Trp)
Genomic name (hg19) chr7:g.117180338C>T    UCSC    gnomAD
#Exon/intron exon 8
Legacy Name R352W
Class disease-causing
Subclass CFTR-RD-causing
WT sequence CATTGTTCTGCGCATGGCGGTCACT C GGCAATTTCCCTGGGCTGTACAAAC
Mutant sequence CATTGTTCTGCGCATGGCGGTCACT T GGCAATTTCCCTGGGCTGTACAAAC


External sources:
dbSNP
rs193922497




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 0.00156 0.03 1
VUS1 VUS5 VUS5 VUS5

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




No patient found in CFTR-NGS catalogue


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

TOTAL NUMBER OF PATIENTS 7
CFTR-RD7
  • Aquagenic palmoplantar keratoderma  2
  • Bronchiectasis  1
  • CBAVD  2
  • Other  2



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
Other 5813heterozygotevarying clinical consequence- Undef
Other 4530heterozygoteVUS5 - Trans
CBAVD 1272heterozygoteCF-causing- Undef
CBAVD 1389heterozygoteCF-causing- Undef
Bronchiectasis 4870heterozygoteVUS3- Undef
CFTR-RD-causing- Undef
Aquagenic palmoplantar keratoderma 5302heterozygoteVUS3- Undef
Aquagenic palmoplantar keratoderma 5785heterozygoteCF-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.