Submissions for variant NM_000492.3(CFTR):c.3458T>A (p.Val1153Glu) (rs397508567)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Clinical Services Laboratory,Illumina	RCV000577089	SCV000916189	uncertain significance	Cystic fibrosis	2018-08-17	criteria provided, single submitter	clinical testing	The CFTR c.3458T>A (p.Val1153Glu) missense variant has been reported in four individuals, including in a compound heterozygous state with an intron variant in one individual with congenital bilateral absence of the vas deference (CBAVD), and in a heterozygous state without a second identified variant in one individual with cystic fibrosis, in one individual with CBAVD, and in one individual with allergic bronchopulmonary aspergillosis (Dörk et al. 1997; Padoan et al. 2002; Ratbi et al. 2007; Lebecque et al. 2011). Control data are unavailable for this variant, which is reported at a frequency of 0.00008 in the European (non-Finnish) population of the Exome Aggregation Consortium. Residue Val1153 is located in transmembrane domain 12 of the CFTR channel, and expressing an alanine substitution at this residue in patch excised inside-out macropatches and single-channel patches from Xenopus oocytes resulted in altered pore properties and suggested that residue 1153 is located toward the intracellular side of the channel pore (Cui et al. 2012). Evidence for this variant is limited, and individuals with this variant in different molecular states have been reported with variable CFTR-related phenotypes. Therefore, the p.Val1153Glu variant is classified as a variant of unknown significance but suspicious for pathogenicity for CFTR-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000577089	SCV000679440	not provided	Cystic fibrosis		no assertion provided	literature only