Variant NM_000492.4:c.328G>C


Variant details:
Name NM_000492.4:c.328G>C
Protein name NP_000483.3:p.(Asp110His)
Genomic name (hg19) chr7:g.117171007G>C    UCSC    gnomAD
#Exon/intron exon 4
Legacy Name D110H
Class disease-causing
Subclass varying clinical consequence
WT sequence ACTGGGAAGAATCATAGCTTCCTAT G ACCCGGATAACAAGGAGGAACGCTC
Mutant sequence ACTGGGAAGAATCATAGCTTCCTAT C ACCCGGATAACAAGGAGGAACGCTC


External sources:
dbSNP
rs113993958


Functional studies:


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


clinical and functional data are provided by Vertex


Pathogenicity predictions:
AGVGD MAPP SIFT PPH2
C65 0.00021 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


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

TOTAL NUMBER OF PATIENTS 12
CF 5
CFTR-RD6
  • CBAVD  5
  • Other  1
Pending 1



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
CF 1251heterozygoteCF-causing - Trans
CF 1743heterozygoteCF-causing- Undef
CF 4862heterozygoteCF-causing- Undef
CF 1311heterozygoteCF-causing - Trans
CF 1273heterozygoteCF-causing - Trans
CBAVD 4921heterozygoteCF-causing - Trans
CBAVD 5047heterozygotevarying clinical consequence- Undef
CBAVD 1679heterozygotevarying clinical consequence- Undef
CBAVD 1500heterozygoteCF-causing- Undef
CBAVD 1471homozygotec.328G>C - p.(Asp110His) - Trans
Pending 4945heterozygoteCF-causing - Trans
Other 4547heterozygoteCF-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.