Variant NM_000492.4:c.346G>A


Variant details:
Name NM_000492.4:c.346G>A
Protein name NP_000483.3:p.(Glu116Lys)
Genomic name (hg19) chr7:g.117171025G>A    UCSC    gnomAD
#Exon/intron exon 4
Legacy Name E116K
Class disease-causing
WT sequence TTCCTATGACCCGGATAACAAGGAG G AACGCTCTATCGCGATTTATCTAGG
Mutant sequence TTCCTATGACCCGGATAACAAGGAG A AACGCTCTATCGCGATTTATCTAGG


External sources:
dbSNP
rs397508571


Functional studies:


Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
Hammerle et al, 2001 11278813 ✓ ✓ ✓


« ✓ » 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
C0 0.1958 0.17 0.999
VUS1 VUS1 VUS2 VUS5

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




No patient found in CFTR-NGS catalogue


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

TOTAL NUMBER OF PATIENTS 2
CF 1
CFTR-RD1
  • Other  1



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
Other 315heterozygotevarying clinical consequence- Undef
CF 1018heterozygoteCF-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.