Variant NM_000492.4:c.3194T>C


Variant details:
Name NM_000492.4:c.3194T>C
Protein name NP_000483.3:p.(Leu1065Pro)
Genomic name (hg19) chr7:g.117251689T>C    UCSC    gnomAD
#Exon/intron exon 20
Legacy Name L1065P
Class disease-causing
Subclass CF-causing
WT sequence ACAAGCTTAAAAGGACTATGGACAC T TCGTGCCTTCGGACGGCAGCCTTAC
Mutant sequence ACAAGCTTAAAAGGACTATGGACAC C TCGTGCCTTCGGACGGCAGCCTTAC


External sources:
dbSNP
rs121909036


Functional studies:


Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
Seibert et al, 1996 8662892 ✓ ✓
Cotten et al, 1996 8702904 ✓
Van Goor et al, 2014 23891399 ✓ ✓ ✓
Sosnay et al, 2013 23974870 ✓ ✓


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




Pathogenicity predictions:
AGVGD MAPP SIFT PPH2
C25 0.00047 0.01 0.996
VUS2 VUS5 VUS5 VUS5

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




No patient found in CFTR-NGS catalogue


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

TOTAL NUMBER OF PATIENTS 4
CF 4



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
CF 181heterozygoteCF-causing - Trans
CF 2363heterozygoteCF-causing- Undef
CF 2797heterozygoteCF-causing - Trans
CF 4237heterozygoteCF-causing - 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.