Variant NM_000492.4:c.509G>A


Variant details:
Name NM_000492.4:c.509G>A
Protein name NP_000483.3:p.(Arg170His)
Genomic name (hg19) chr7:g.117174349G>A    UCSC    gnomAD
#Exon/intron exon 5
Legacy Name R170H
Class disease-causing
Subclass CFTR-RD-causing
WT sequence TTTTAGACTTTAAAGCTGTCAAGCC G TGTTCTAGATAAAATAAGTATTGGA
Mutant sequence TTTTAGACTTTAAAGCTGTCAAGCC A TGTTCTAGATAAAATAAGTATTGGA


External sources:
dbSNP
rs1800079


Functional studies:


Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
LaRusch et al, 2014 25033378 ✓ ✓ ✓


« ✓ » 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
C0 0.00638 0.01 0.999
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
CFTR-RD12
  • CBAVD  9
  • Other  2
  • Pancreatitis  1



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
CBAVD 419heterozygoteVUS3- Undef
CF-causing- Undef
CBAVD 2525heterozygoteCF-causing- Undef
CBAVD 1472heterozygoteCF-causing- Undef
CBAVD 1132heterozygotevarying clinical consequence- Undef
CBAVD 553heterozygoteCF-causing- Undef
CBAVD 517heterozygoteCF-causing- Undef
CBAVD 504heterozygoteCF-causing- Undef
CBAVD 456heterozygoteCF-causing - Trans
CBAVD 5603heterozygoteCF-causing- Undef
Other 5381heterozygoteCF-causing- Undef
Other 5743heterozygoteCF-causing - Trans
VUS1- Undef
Pancreatitis 5154heterozygoteVUS3- Undef
CFTR-RD-causing- Undef


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.