Variant NM_000492.4:c.1801A>T


Variant details:
Name NM_000492.4:c.1801A>T
Protein name NP_000483.3:p.(Ile601Phe)
Genomic name (hg19) chr7:g.117232022A>T    UCSC    gnomAD
#Exon/intron exon 14
Legacy Name I601F
Class disease-causing
Subclass varying clinical consequence
WT sequence TAAACTGATGGCTAACAAAACTAGG A TTTTGGTCACTTCTAAAATGGAACA
Mutant sequence TAAACTGATGGCTAACAAAACTAGG T TTTTGGTCACTTCTAAAATGGAACA


External sources:
dbSNP
rs397508306


Functional studies:


Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
Vankeerberghen et al, 1998 9736778 ✓


« ✓ » 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 0.00741 0 0.997
VUS1 VUS5 VUS5 VUS5

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




No patient found in CFTR-NGS catalogue


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

TOTAL NUMBER OF PATIENTS 12
CF 2
CFTR-RD4
  • CBAVD  2
  • Other  1
  • Pancreatitis  1
Fetal bowel anomalies 1
Pending 1
Pending (NBS) 3
Pending non-CF 1



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
CBAVD 626heterozygoteCFTR-RD-causing - Trans
CBAVD 2348heterozygoteCF-causing- Undef
Pending (NBS) 3713heterozygoteCF-causing - Trans
Pending (NBS) 5399heterozygoteCF-causing- Undef
Pending (NBS) 726heterozygoteCF-causing - Trans
Fetal bowel anomalies 5147heterozygoteCF-causing - Trans
Pancreatitis 4789heterozygoteCF-causing- Undef
CF 5116heterozygoteCF-causing- Undef
CF 1293heterozygoteCF-causing- Undef
Pending 5868heterozygoteCF-causing- Undef
Other 4813heterozygoteCF-causing- Undef
Pending non-CF 4515heterozygotevarying clinical consequence - 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.