Submissions for variant NM_000492.4(CFTR):c.442del (p.Ile148fs)

dbSNP: rs121908770

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR2	RCV000056392	SCV000071488	pathogenic	Cystic fibrosis	2017-03-17	reviewed by expert panel	research
Eurofins Ntd Llc (ga)	RCV000727641	SCV000854927	pathogenic	not provided	2017-09-22	criteria provided, single submitter	clinical testing
CFTR-France	RCV000056392	SCV001169342	pathogenic	Cystic fibrosis	2018-01-29	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000056392	SCV001193808	pathogenic	Cystic fibrosis	2019-11-12	criteria provided, single submitter	clinical testing	NM_000492.3(CFTR):c.442delA(I148Lfs*5, aka 574delA) is classified as pathogenic in the context of cystic fibrosis and is associated with the classic form of disease. Sources cited for classification include the following: PMID 15371903, 1379210, 23974870, and 18456578. Classification of NM_000492.3(CFTR):c.442delA(I148Lfs*5, aka 574delA) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening.‚Äã
Labcorp Genetics (formerly Invitae), Labcorp	RCV000056392	SCV001580423	pathogenic	Cystic fibrosis	2023-04-23	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 53948). This variant is also known as c.574delA. This premature translational stop signal has been observed in individuals with cystic fibrosis (PMID: 27728908; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile148Leufs*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).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000056392	SCV005725966	pathogenic	Cystic fibrosis	2024-11-25	criteria provided, single submitter	clinical testing	Variant summary: CFTR c.442delA (p.Ile148LeufsX5), also known as 574delA, 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. The variant was absent in 250496 control chromosomes. c.442delA has been reported in the literature in a cohort affected with Cystic Fibrosis (example, Chernykh_2023). The following publication has been ascertained in the context of this evaluation (PMID: 38003474). ClinVar contains an entry for this variant (Variation ID: 53948). Based on the evidence outlined above, the variant was classified as pathogenic.
Natera, Inc.	RCV001826687	SCV002080140	pathogenic	CFTR-related disorder	2017-03-17	no assertion criteria provided	clinical testing