Variant NM_000492.4:c.1013C>T


Variant details:
Name NM_000492.4:c.1013C>T
Protein name NP_000483.3:p.(Thr338Ile)
Genomic name (hg19) chr7:g.117180297C>T    UCSC    gnomAD
#Exon/intron exon 8
Legacy Name T338I
Class disease-causing
Subclass CFTR-RD-causing
WT sequence GGAATCATCCTCCGGAAAATATTCA C CACCATCTCATTCTGCATTGTTCTG
Mutant sequence GGAATCATCCTCCGGAAAATATTCA T CACCATCTCATTCTGCATTGTTCTG


External sources:
dbSNP
rs77409459


Functional studies:


Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
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
IVA yesnoyesno
TEZ-IVA yesnoyesno
ELX-TEZ-IVA yesnoyesno


clinical and functional data are provided by Vertex


Pathogenicity predictions:
AGVGD MAPP SIFT PPH2
C65 1e-05 0 0.999
VUS5 VUS5 VUS5 VUS5

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




No patient found in CFTR-NGS catalogue


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

TOTAL NUMBER OF PATIENTS 13
Asymptomatic compound heterozygote 1
CF 2
CFTR-RD5
  • CBAVD  4
  • Other  1
Pending (NBS) 5



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
CBAVD 508heterozygoteCFTR-RD-causing - Trans
CFTR-RD-causing - Trans
CFTR-RD-causing - Trans
CBAVD 2885heterozygoteCFTR-RD-causing- Undef
CBAVD 534heterozygoteCF-causing - Trans
CBAVD 522heterozygoteCF-causing - Trans
Other 547heterozygoteCF-causing - Trans
Pending (NBS) 5237heterozygoteCF-causing - Trans
Pending (NBS) 5241heterozygoteCF-causing - Trans
Pending (NBS) 5817heterozygoteCF-causing- Undef
Pending (NBS) 826heterozygoteCF-causing - Trans
Pending (NBS) 5236heterozygoteCF-causing - Trans
CF 5511heterozygoteCF-causing - Trans
CF 5510heterozygoteCF-causing - Trans
Asymptomatic compound heterozygote 5240heterozygoteCF-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.