Variant NM_000492.4:c.91C>T


Variant details:
Name NM_000492.4:c.91C>T
Protein name NP_000483.3:p.(Arg31Cys)
Genomic name (hg19) chr7:g.117144344C>T    UCSC    gnomAD
#Exon/intron exon 2
Legacy Name R31C ; 223C/T
Class VUS
Subclass VUS4
WT sequence AATTTTGAGGAAAGGATACAGACAG C GCCTGGAATTGTCAGACATATACCA
Mutant sequence AATTTTGAGGAAAGGATACAGACAG T GCCTGGAATTGTCAGACATATACCA


External sources:
860
1001
 dbSNP
rs1800073


Functional studies:


Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
Jurkuvenaite et al, 2006 16339147 ✓ ✓ ✓
Sosnay et al, 2013 23974870 ✓ ✓


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




Pathogenicity predictions:
AGVGD MAPP SIFT PPH2
C15 0.00316 0.02 0.989
VUS1 VUS5 VUS5 VUS5

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




2 individuals carrying this variant are reported in CFTR-NGS catalogue


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

TOTAL NUMBER OF PATIENTS 17
Asymptomatic compound heterozygote 4
CF 2
CFTR-RD10
  • Bronchiectasis  3
  • CBAVD  1
  • Pancreatitis  6
Pending 1



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
Asymptomatic compound heterozygote 922heterozygote
Asymptomatic compound heterozygote 5525heterozygoteVUS3- Undef
Asymptomatic compound heterozygote 965heterozygoteCFTR-RD-causing - Trans
Asymptomatic compound heterozygote 4579heterozygoteVUS1 - Trans
Pancreatitis 5115heterozygoteVUS3- Undef
Pancreatitis 5894heterozygoteCFTR-RD-causing- Undef
Pancreatitis 5108heterozygoteCF-causing- Undef
Pancreatitis 1851heterozygoteCFTR-RD-causing - Trans
Pancreatitis 1168heterozygote
Pancreatitis 964heterozygoteCFTR-RD-causing - Trans
CF 2546heterozygoteCF-causing- Undef
CF 975heterozygoteCF-causing- Undef
Bronchiectasis 4253heterozygote
Bronchiectasis 2590heterozygoteCF-causing- Undef
Bronchiectasis 5043heterozygoteCF-causing- Undef
CBAVD 2400heterozygote
Pending 3089heterozygote


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.