Variant NM_000492.4:c.1841A>G


Variant details:
Name NM_000492.4:c.1841A>G
Protein name NP_000483.3:p.(Asp614Gly)
Genomic name (hg19) chr7:g.117232062A>G    UCSC    gnomAD
#Exon/intron exon 14
Legacy Name D614G
Class disease-causing
Subclass varying clinical consequence
WT sequence AAAATGGAACATTTAAAGAAAGCTG A CAAAATATTAATTTTGCATGAAGGT
Mutant sequence AAAATGGAACATTTAAAGAAAGCTG G CAAAATATTAATTTTGCATGAAGGT


External sources:
dbSNP
rs201124247


Functional studies:


Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
Vankeerberghen et al, 1998 9736778 ✓
Pasyk et al, 1998 9822639 ✓ ✓ ✓
Sosnay et al, 2013 23974870 ✓ ✓


« ✓ » 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-IVA yesnoyesno
ELX-TEZ-IVA yesnoyesno


clinical and functional data are provided by Vertex


Pathogenicity predictions:
AGVGD MAPP SIFT PPH2
C65 0.00018 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


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

TOTAL NUMBER OF PATIENTS 6
CFTR-RD4
  • CBAVD  2
  • Pancreatitis  2
Pending (NBS) 2



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
CBAVD 1474heterozygoteCFTR-RD-causing- Undef
CBAVD 4949heterozygoteCF-causing- Undef
Pending (NBS) 5327heterozygoteCF-causing - Trans
Pending (NBS) 4288heterozygoteCF-causing - Trans
Pancreatitis 5307heterozygoteCFTR-RD-causing- Undef
Pancreatitis 4614heterozygotevarying 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.