Variant NM_000492.4:c.494T>C


Variant details:
Name NM_000492.4:c.494T>C
Protein name NP_000483.3:p.(Leu165Ser)
Genomic name (hg19) chr7:g.117174334T>C    UCSC    gnomAD
#Exon/intron exon 5
Legacy Name L165S
Class disease-causing
Subclass CF-causing
WT sequence AACTTTCCATTTTTCTTTTAGACTT T AAAGCTGTCAAGCCGTGTTCTAGAT
Mutant sequence AACTTTCCATTTTTCTTTTAGACTT C AAAGCTGTCAAGCCGTGTTCTAGAT


External sources:
dbSNP
rs397508736




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
C65 4e-05 0 1
VUS5 VUS5 VUS5 VUS5

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




No patient found in CFTR-NGS catalogue


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

TOTAL NUMBER OF PATIENTS 9
CF 8
CFTR-RD1
  • CRS-NP  1



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
CF 284heterozygotevarying clinical consequence- Undef
CF 842heterozygoteCF-causing- Undef
CF 2052heterozygoteCF-causing- Undef
CF 3306heterozygoteCF-causing - Trans
CF 3385heterozygoteCF-causing - Trans
CF 5348heterozygoteCF-causing - Trans
CF 5335heterozygoteCF-causing - Trans
CF 4074heterozygoteCF-causing- Undef
CRS-NP 3284heterozygotevarying clinical consequence- 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.