Submissions for variant NM_000492.4(CFTR):c.3889dup (p.Ser1297fs)

dbSNP: rs121908808

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR2	RCV000047018	SCV000071484	pathogenic	Cystic fibrosis	2017-03-17	reviewed by expert panel	research
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000507350	SCV000601110	pathogenic	not provided	2016-09-30	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000047018	SCV000696998	pathogenic	Cystic fibrosis	2017-07-18	criteria provided, single submitter	clinical testing	Variant summary: The CFTR c.3889dupT (p.Ser1297Phefs) variant results in a premature termination codon, predicted to cause a truncated or absent CFTR 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 (e.g. c.3937C>T, p.Gln1313X; c.4077_4080delinsAA, p.Val1360fs). One in silico tool predicts a damaging outcome for this variant. This variant was found in 3/119932 control chromosomes at a frequency of 0.000025, which does not exceed the estimated maximal expected allele frequency of a pathogenic CFTR variant (0.0129603). This variant was reported in multiple CF patients (Sosnay_Nature Genetics_2013, Behar_Mol Genet Gen Med_2017) and has been reported by reputable databases/clinical labs as pathogenic. Taken together, this variant is classified as pathogenic.
Mendelics	RCV000047018	SCV000886211	pathogenic	Cystic fibrosis	2018-11-05	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001004511	SCV001163556	pathogenic	Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation		criteria provided, single submitter	clinical testing
CFTR-France	RCV000047018	SCV001169350	pathogenic	Cystic fibrosis	2018-01-29	criteria provided, single submitter	curation
Invitae	RCV000047018	SCV001581983	pathogenic	Cystic fibrosis	2023-09-06	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser1297Phefs*5) 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 (rs749871110, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with cystic fibrosis (PMID: 7684644, 23974870). This variant is also known as 4016 insT or c.3884_3885insT. ClinVar contains an entry for this variant (Variation ID: 53841). For these reasons, this variant has been classified as Pathogenic.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV000047018	SCV002507320	pathogenic	Cystic fibrosis	2021-07-22	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000047018	SCV002573868	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, PM2_SUP, PM3_VSTR
Baylor Genetics	RCV003474595	SCV004213355	pathogenic	Bronchiectasis with or without elevated sweat chloride 1	2023-09-27	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000047018	SCV004805434	pathogenic	Cystic fibrosis	2024-03-25	criteria provided, single submitter	research
Counsyl	RCV000047018	SCV000486295	pathogenic	Cystic fibrosis	2016-05-04	no assertion criteria provided	clinical testing
Natera, Inc.	RCV001826676	SCV002075904	pathogenic	CFTR-related disorders	2017-03-17	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001826676	SCV002507404	pathogenic	CFTR-related disorders	2021-07-22	no assertion criteria provided	clinical testing