Submissions for variant NM_000492.4(CFTR):c.3124C>T (p.Gln1042Ter)

gnomAD frequency: 0.00001  dbSNP: rs397508500

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR2	RCV000576454	SCV000677619	pathogenic	Cystic fibrosis	2017-03-17	reviewed by expert panel	research
CFTR-France	RCV000576454	SCV001169289	pathogenic	Cystic fibrosis	2018-01-29	criteria provided, single submitter	curation
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000576454	SCV001426803	pathogenic	Cystic fibrosis	2020-07-20	criteria provided, single submitter	clinical testing	Variant summary: CFTR c.3124C>T (p.Gln1042X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 250866 control chromosomes. c.3124C>T has been reported in the literature in individuals affected with Cystic Fibrosis (e.g. Escotte_2002, Audrezet_2008, Oca_2009, Dorfman_2010, Middleton_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. Two expert panels have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both cited the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000576454	SCV004446620	pathogenic	Cystic fibrosis	2023-12-25	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln1042*) 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 present in population databases (rs397508500, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with cystic fibrosis (PMID: 19833837). ClinVar contains an entry for this variant (Variation ID: 53654). For these reasons, this variant has been classified as Pathogenic.
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000576454	SCV000679031	not provided	Cystic fibrosis		no assertion provided	literature only
Natera, Inc.	RCV001826656	SCV002083595	pathogenic	CFTR-related disorder	2017-03-17	no assertion criteria provided	clinical testing