Submissions for variant NM_000492.4(CFTR):c.3304A>T (p.Arg1102Ter)

dbSNP: rs397508536

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR2	RCV000046861	SCV000245971	pathogenic	Cystic fibrosis	2017-03-17	reviewed by expert panel	research
CFTR-France	RCV000046861	SCV001169293	pathogenic	Cystic fibrosis	2018-01-29	criteria provided, single submitter	curation
Labcorp Genetics (formerly Invitae), Labcorp	RCV000046861	SCV001591326	pathogenic	Cystic fibrosis	2022-02-04	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg1102*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with cystic fibrosis (PMID: 22892530). ClinVar contains an entry for this variant (Variation ID: 53713). For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center	RCV000046861	SCV002574012	pathogenic	Cystic fibrosis	2022-09-05	criteria provided, single submitter	curation	This variant was identified in 2 unrelated patients 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
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000046861	SCV003929023	pathogenic	Cystic fibrosis	2023-04-25	criteria provided, single submitter	clinical testing	Variant summary: CFTR c.3304A>T (p.Arg1102X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Variants downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251048 control chromosomes (gnomAD). c.3304A>T has been reported in the literature in individuals affected with Cystic Fibrosis (e.g. Sobczynska-Tomaszewska_2013, Girardet_2007, Raraigh_2022, McCague_2019). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 17850636, 30888834, 34782259, 22892530). Five ClinVar submitters, including one expert panel (CFTR2), have assessed the variant since 2014: all five submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Johns Hopkins Genomics, Johns Hopkins University	RCV000046861	SCV004239090	pathogenic	Cystic fibrosis	2023-08-09	criteria provided, single submitter	clinical testing	Disease-causing CFTR variant. See www.CFTR2.org for phenotype information.
Natera, Inc.	RCV001826662	SCV002083630	pathogenic	CFTR-related disorder	2017-03-17	no assertion criteria provided	clinical testing