Variant NM_000492.4:c.1721C>A


Variant details:
Name NM_000492.4:c.1721C>A
Protein name NP_000483.3:p.(Pro574His)
Genomic name (hg19) chr7:g.117230448C>A    UCSC    gnomAD
#Exon/intron exon 13
Legacy Name P574H
Class disease-causing
Subclass varying clinical consequence
WT sequence GCTGATTTGTATTTATTAGACTCTC C TTTTGGATACCTAGATGTTTTAACA
Mutant sequence GCTGATTTGTATTTATTAGACTCTC A TTTTGGATACCTAGATGTTTTAACA


External sources:
dbSNP
rs121908758


Functional studies:


Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
Sheppard et al, 1995 7534226 ✓ ✓
Champigny et al, 1995 7540133 ✓ ✓ ✓
Cotten et al, 1996 8702904 ✓


« ✓ » 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-IVAnononono
ELX-TEZ-IVA yesnoyesno


clinical and functional data are provided by Vertex


Pathogenicity predictions:
AGVGD MAPP SIFT PPH2
C25 0.00488 0 1
VUS2 VUS5 VUS5 VUS5

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




No patient found in CFTR-NGS catalogue


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

TOTAL NUMBER OF PATIENTS 4
CF 1
CFTR-RD2
  • CBAVD  2
Pending (NBS) 1



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
CBAVD 1327heterozygoteVUS2 - Trans
CF-causing - Trans
CBAVD 4484heterozygoteCF-causing - Trans
Pending (NBS) 3628heterozygoteCF-causing- Undef
CF 3850heterozygoteCF-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.