Submissions for variant NM_000492.4(CFTR):c.3937C>T (p.Gln1313Ter)

dbSNP: rs121909026

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR2	RCV000007600	SCV000071543	pathogenic	Cystic fibrosis	2017-03-17	reviewed by expert panel	research
CFTR-France	RCV000007600	SCV001169365	pathogenic	Cystic fibrosis	2018-01-29	criteria provided, single submitter	curation
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000007600	SCV001432103	pathogenic	Cystic fibrosis	2020-08-17	criteria provided, single submitter	clinical testing	Variant summary: CFTR c.3937C>T (p.Gln1313X) 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 was absent in 250482 control chromosomes. c.3937C>T has been reported in the literature in multiple individuals affected with Cystic Fibrosis (example, Audrezet_1993, Alonso_2007, Schrijver_2005, desGeorges_2004, Dorfman_2010, Krenkova_2012). These data indicate that the variant is very likely to be associated with disease. Three clinical diagnostic laboratories and one expert panel (CFTR2) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000007600	SCV001584845	pathogenic	Cystic fibrosis	2024-01-30	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln1313*) 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: 7683952, 22658665, 23974870). This variant is also known as c.4069C>T. ClinVar contains an entry for this variant (Variation ID: 7180). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV000007600	SCV002624320	pathogenic	Cystic fibrosis	2015-06-29	criteria provided, single submitter	clinical testing	The p.Q1313* pathogenic mutation (also known as c.3937C>T, c.4069C>T and p.Q1313X) is located in coding exon 24 of the CFTR gene. In one study, this mutation was detected in homozygous state in a patient with pancreatic insufficiency and severe symptoms (Audrezet MP et. al. Hum. Molec Genet. 1993;2(1):51-54). This mutation is associated with decreased lung function (mean FEV 71%), elevated sweat chloride levels, pancreatic insufficiency, and pseudomonas (Sosnay PR et al. Nat Genet. 2013;45(10):1160-1167, Supplementary Table and The Clinical and Functional Translation of CFTR (CFTR2); available at http://cftr2.org. Accessed July 27, 2015). In addition to the clinical data presented in the literature, since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Baylor Genetics	RCV003473032	SCV004213529	pathogenic	Bronchiectasis with or without elevated sweat chloride 1	2023-04-12	criteria provided, single submitter	clinical testing
OMIM	RCV000007600	SCV000027801	pathogenic	Cystic fibrosis	2018-04-09	no assertion criteria provided	literature only
Counsyl	RCV000007600	SCV000220756	pathogenic	Cystic fibrosis	2016-09-09	no assertion criteria provided	clinical testing
Natera, Inc.	RCV001826441	SCV002075915	pathogenic	CFTR-related disorder	2017-03-17	no assertion criteria provided	clinical testing