Variant NM_000492.4:c.1673T>C


Variant details:
Name NM_000492.4:c.1673T>C
Protein name NP_000483.3:p.(Leu558Ser)
Genomic name (hg19) chr7:g.117227881T>C    UCSC    gnomAD
#Exon/intron exon 12
Legacy Name L558S
Class disease-causing
Subclass CF-causing
WT sequence GGAGGTCAACGAGCAAGAATTTCTT T AGCAAGGTGAATAACTAATTATTGG
Mutant sequence GGAGGTCAACGAGCAAGAATTTCTT C AGCAAGGTGAATAACTAATTATTGG


External sources:
dbSNP
rs193922504


Functional studies:


Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
Sosnay et al, 2013 23974870 ✓


« ✓ » indicates the type of analysis performed and not the results




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


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

TOTAL NUMBER OF PATIENTS 7
CF 6
CFTR-RD1
  • Other  1



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
CF 561heterozygoteCF-causing - Trans
CF 718heterozygoteCF-causing - Trans
CF 1041heterozygoteCF-causing - Trans
CF 5448heterozygoteCF-causing- Undef
CF 2508heterozygoteCF-causing- Undef
CF 3684heterozygoteCF-causing- Undef
Other 853heterozygotevarying clinical consequence - 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.