Variant NM_000492.4:c.1367T>C


Variant details:
Name NM_000492.4:c.1367T>C
Protein name NP_000483.3:p.(Val456Ala)
Genomic name (hg19) chr7:g.117188852T>C    UCSC    gnomAD
#Exon/intron exon 10
Legacy Name V456A
Class disease-causing
WT sequence ATAGAAAGAGGACAGTTGTTGGCGG T TGCTGGATCCACTGGAGCAGGCAAG
Mutant sequence ATAGAAAGAGGACAGTTGTTGGCGG C TGCTGGATCCACTGGAGCAGGCAAG


External sources:
dbSNP
rs193922500




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
0.01 0.825
no class no class VUS5 VUS4

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




No patient found in CFTR-NGS catalogue


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

TOTAL NUMBER OF PATIENTS 3
CF 1
CFTR-RD2
  • CBAVD  1
  • Pancreatitis  1



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
CBAVD 5002heterozygoteCF-causing- Undef
CF 5113heterozygoteCF-causing- Undef
Pancreatitis 5003heterozygote


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.