Variant NM_000492.4:c.3458T>A


Variant details:
Name NM_000492.4:c.3458T>A
Protein name NP_000483.3:p.(Val1153Glu)
Genomic name (hg19) chr7:g.117254757T>A    UCSC    gnomAD
#Exon/intron exon 21
Legacy Name V1153E
Class disease-causing
Subclass CFTR-RD-causing
WT sequence TGGGCTGTAAACTCCAGCATAGATG T GGATAGCTTGGTAAGTCTTATCATC
Mutant sequence TGGGCTGTAAACTCCAGCATAGATG A GGATAGCTTGGTAAGTCTTATCATC


External sources:
dbSNP
rs397508567




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 2e-05 0.03 0.983
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
Asymptomatic compound heterozygote 1
CFTR-RD5
  • CBAVD  5
Pending (NBS) 1



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
CBAVD 551heterozygoteCF-causing- Undef
CBAVD 938heterozygoteCF-causing - Trans
CBAVD 1386heterozygote
CBAVD 4980heterozygoteCF-causing- Undef
CBAVD 5889heterozygoteCF-causing- Undef
Pending (NBS) 4643heterozygoteCF-causing - Trans
Asymptomatic compound heterozygote 4285heterozygoteVUS2 - 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.