CFTR-France

Variant details:
Name	NM_000492.4:c.1666A>G
Protein name	NP_000483.3:p.(Ile556Val)
Genomic name (hg19)	chr7:g.117227874A>G UCSC gnomAD
#Exon/intron	exon 12
Legacy Name	I556V
Class	disease-causing
Subclass	CFTR-RD-causing
WT sequence	ACTGAGTGGAGGTCAACGAGCAAGA A TTTCTTTAGCAAGGTGAATAACTAA
Mutant sequence	ACTGAGTGGAGGTCAACGAGCAAGA G TTTCTTTAGCAAGGTGAATAACTAA

External sources:
	Not found	dbSNP rs75789129

Reference	PMID	Splicing	mRNA level	Maturation	Localization	Channel fonction (Cl-)	Bicarbonate
Lee et al, 2003	12952861			✓		✓	✓

Pathogenicity predictions:
AGVGD	MAPP	SIFT	PPH2
C15	0.00977	0.08	0.334
VUS1	VUS5	VUS4	VUS2

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

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

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

TOTAL NUMBER OF PATIENTS	3
Asymptomatic compound heterozygote	1
CFTR-RD	2 CBAVD 1 Pancreatitis 1

Detailed genotypes:
Phenotype	Patient ID	Variant status	Additional variants
Asymptomatic compound heterozygote	4685	heterozygote	CF-causing - Trans
CBAVD	1345	heterozygote	CFTR-RD-causing- Undef
Pancreatitis	5152	homozygote	c.1666A>G - p.(Ile556Val) - 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.

Go to