Submissions for variant NM_000492.4(CFTR):c.1703del (p.Leu568fs)

dbSNP: rs397508274

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR2	RCV000576635	SCV000677594	pathogenic	Cystic fibrosis	2017-03-17	reviewed by expert panel	research
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000755914	SCV000883569	pathogenic	not provided	2017-05-31	criteria provided, single submitter	clinical testing	The CFTR c.1703delT, p.Leu568fs variant (also known as 1833delT) has been reported in patients with cystic fibrosis (SickKids CFTR database, CFTR2 databases), but the clinical symptoms were not described. It is listed in the ClinVar database (Variation ID: 53349) and the dbSNP variant database (rs397508274), but not observed in the general population databases (1000 Genomes Project, Exome Variant Server, Exome Aggregation Consortium). The variant introduces a frameshift, and is predicted to result in a truncated protein or an absent transcript. Based on the above information, the variant is classified as pathogenic, with uncertain clinical severity. References: CFTR2 database: http://cftr2.org SickKids CFTR database: http://www.genet.sickkids.on.ca/cftr/MutationDetailPage.external?sp=292
CFTR-France	RCV000576635	SCV001169396	pathogenic	Cystic fibrosis	2018-01-29	criteria provided, single submitter	curation
Institute of Human Genetics, University of Leipzig Medical Center	RCV000576635	SCV002574014	pathogenic	Cystic fibrosis	2022-09-05	criteria provided, single submitter	curation	This variant was identified in 1 patient with a clinically confirmed diagnosis of cystic fibrosis. The variant was classified in the context of a project re-classifying variants in the German Cystic Fibrosis Registry (Muko.e.V.). Link: https://www.muko.info/angebote/qualitaetsmanagement/register/cf-einrichtungen/mukoweb. Criteria applied: PVS1, PM3_STR, PM2_SUP, PP4
Labcorp Genetics (formerly Invitae), Labcorp	RCV000576635	SCV004295545	pathogenic	Cystic fibrosis	2023-08-03	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 53349). This premature translational stop signal has been observed in individual(s) with clinical features of CFTR-related conditions (PMID: 23974870). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu568Cysfs*4) in the CFTR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922).
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000576635	SCV000678920	not provided	Cystic fibrosis		no assertion provided	literature only
Natera, Inc.	RCV001831734	SCV002080653	pathogenic	CFTR-related disorder	2017-03-17	no assertion criteria provided	clinical testing