Variant NM_000492.4:c.1646G>A


Variant details:
Name NM_000492.4:c.1646G>A
Protein name NP_000483.3:p.(Ser549Asn)
Genomic name (hg19) chr7:g.117227854G>A    UCSC    gnomAD
#Exon/intron exon 12
Legacy Name S549N
Class disease-causing
Subclass CF-causing
WT sequence CTTGGAGAAGGTGGAATCACACTGA G TGGAGGTCAACGAGCAAGAATTTCT
Mutant sequence CTTGGAGAAGGTGGAATCACACTGA A TGGAGGTCAACGAGCAAGAATTTCT


External sources:
dbSNP
rs121908755


Functional studies:


Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
Yu et al, 2012 22293084 ✓ ✓ ✓
Sosnay et al, 2013 23974870 ✓ ✓
Sharma et al, 2014 25042876 ✓ ✓


« ✓ » 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 yes yesno yes
TEZ-IVA yesnoyesno
ELX-TEZ-IVA yesnoyesno


clinical and functional data are provided by Vertex


Pathogenicity predictions:
AGVGD MAPP SIFT PPH2
C45 0.00166 0 1
VUS4 VUS5 VUS5 VUS5

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




No patient found in CFTR-NGS catalogue


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

TOTAL NUMBER OF PATIENTS 5
CF 2
CFTR-RD3
  • CBAVD  2
  • Pancreatitis  1



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
CBAVD 1340heterozygoteCFTR-RD-causing- Undef
CFTR-RD-causing- Undef
CFTR-RD-causing- Undef
CBAVD 3309heterozygotevarying clinical consequence- Undef
Pancreatitis 2033heterozygoteCFTR-RD-causing- Undef
CFTR-RD-causing- Undef
CF 2597heterozygotevarying clinical consequence- Undef
CF-causing- Undef
CF 3441heterozygoteCF-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.