Submissions for variant NM_000492.4(CFTR):c.233dup (p.Trp79fs)

dbSNP: rs397508360

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR2	RCV000046577	SCV000245982	pathogenic	Cystic fibrosis	2017-03-17	reviewed by expert panel	research
Counsyl	RCV000046577	SCV000485818	pathogenic	Cystic fibrosis	2016-02-18	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000508526	SCV000601074	pathogenic	not provided	2016-09-20	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000508526	SCV000856496	pathogenic	not provided	2017-08-21	criteria provided, single submitter	clinical testing
CFTR-France	RCV000046577	SCV001169560	pathogenic	Cystic fibrosis	2018-01-29	criteria provided, single submitter	curation
Labcorp Genetics (formerly Invitae), Labcorp	RCV000046577	SCV001585590	pathogenic	Cystic fibrosis	2023-12-30	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Trp79Leufs*32) 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). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with cystic fibrosis and chronic pancreatitis (PMID: 15300780, 21520337, 28174639). ClinVar contains an entry for this variant (Variation ID: 53475). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000046577	SCV002103508	pathogenic	Cystic fibrosis	2022-02-28	criteria provided, single submitter	clinical testing	Variant summary: CFTR c.233dupT (p.Trp79LeufsX32) 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 250970 control chromosomes. c.233dupT has been reported in the literature in individuals affected with Cystic Fibrosis or CBAVD. These data indicate that the variant may be associated with disease. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Ambry Genetics	RCV000046577	SCV002732606	pathogenic	Cystic fibrosis	2022-04-04	criteria provided, single submitter	clinical testing	The c.233dupT pathogenic mutation (also known as 365_366insT), located in coding exon 3 of the CFTR gene, results from a duplication of T at nucleotide position 233, causing a translational frameshift with a predicted alternate stop codon (p.W79Lfs*32). This mutation was reported in a individual with cystic fibrosis (CF) and a pathogenic CFTR alteration, as well as in an individual with congenital bilateral absence of the vas deferens (CBAVD) with the 5T variant; however, the phase (whether in cis or trans) is not known for either individual (Alper OM et al. Hum. Mutat., 2004 Oct;24:353; Steiner B et al. Hum. Mutat., 2011 Aug;32:912-20). This mutation was also identified in a homozygous individual with pancreatic insufficient CF (Soe K et al. Clin Case Rep, 2017 Feb;5:139-144). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Baylor Genetics	RCV003473481	SCV004213495	pathogenic	Bronchiectasis with or without elevated sweat chloride 1	2023-11-20	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000046577	SCV004565268	pathogenic	Cystic fibrosis	2024-11-04	criteria provided, single submitter	clinical testing	The CFTR c.233dup; p.Trp79LeufsTer32 variant (rs397508360), also known as 360-365insT, is reported in individuals with cystic fibrosis (see CFTR2 database, Soe 2017), and is reported in ClinVar (Variation ID: 53475). This variant is only found on two alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. This variant causes a frameshift by inserting a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Link to CFTR2 database: https://cftr2.org/ Soe K et al. A rare CFTR mutation associated with severe disease progression in a 10-year-old Hispanic patient. Clin Case Rep. 2017 Jan 19;5(2):139-144. PMID: 28174639.
Natera, Inc.	RCV001826634	SCV002080090	pathogenic	CFTR-related disorder	2017-03-17	no assertion criteria provided	clinical testing