Variant NM_000492.4:c.680T>G


Variant details:
Name NM_000492.4:c.680T>G
Protein name NP_000483.3:p.(Leu227Arg)
Genomic name (hg19)     chr7:g.117175402T>G    UCSC    
Genomic name (hg38) chr7:g.117535348T>G    UCSC
#Exon/intron exon 6
Legacy Name L227R
Class disease-causing
Subclass CF-causing
WT sequence TTACAGGCGTCTGCCTTCTGTGGAC T TGGTTTCCTGATAGTCCTTGCCCTT
Mutant sequence TTACAGGCGTCTGCCTTCTGTGGAC G TGGTTTCCTGATAGTCCTTGCCCTT

Other databases:
dbSNP
rs397508782



Pathogenicity predictors:

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



Response to modulators:


Reference PMID Modulator in vitro / ex vivo data clinical data Patient responsiveness
Burgel et al., 2024 39151434 ELX-TEZ-IVAN.D. yesno



No patient found in CFTR-NGS catalogue


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

TOTAL NUMBER OF PATIENTS 15
CF 13
CFTR-RD2
  • CBAVD  1
  • Pancreatitis  1




Color code:   non disease-causing <   likely benign <   VUS <   likely pathogenic <   disease-causing

Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
CF 158heterozygoteCF-causing- Undef
CF 3666heterozygoteCF-causing- Undef
CF 2802heterozygoteCF-causing- Undef
CF 6252heterozygoteCF-causing - Trans
CF 6026heterozygoteCF-causing - Trans
CF 5114heterozygoteCF-causing- Undef
CF 5098heterozygoteCF-causing- Undef
CF 1226heterozygoteCF-causing- Undef
CF 2011homozygotec.680T>G - p.(Leu227Arg) - Trans
CF 1059homozygotec.680T>G - p.(Leu227Arg) - Trans
CF 1057homozygotec.680T>G - p.(Leu227Arg) - Trans
CF 977homozygotec.680T>G - p.(Leu227Arg) - Trans
CF 5378homozygotec.680T>G - p.(Leu227Arg) - Trans
CBAVD 4646heterozygoteVUS3 - Trans
Pancreatitis 3182heterozygoteCFTR-RD-causing- Undef


Color code:   non disease-causing <   likely benign <   VUS <   likely pathogenic <   disease-causing



            CFTR variants are clustered into five groups (click here for more details about the classification of variants):
  • 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.



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