Submissions for variant NM_000492.4(CFTR):c.803del (p.Asn268fs)

dbSNP: rs121908772

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR2	RCV000047258	SCV000245931	pathogenic	Cystic fibrosis	2017-03-17	reviewed by expert panel	research
Eurofins Ntd Llc (ga)	RCV000790728	SCV000232063	pathogenic	not provided	2013-02-20	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000047258	SCV001194056	pathogenic	Cystic fibrosis	2019-12-04	criteria provided, single submitter	clinical testing	NM_000492.3(CFTR):c.803delA(N268Ifs*17, aka 935delA) is classified as pathogenic in the context of cystic fibrosis. Sources cited for classification include the following: PMID 10993719 and 21416780. Classification of NM_000492.3(CFTR):c.803delA(N268Ifs*17, aka 935delA) 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000047258	SCV001362679	pathogenic	Cystic fibrosis	2019-10-14	criteria provided, single submitter	clinical testing	Variant summary: CFTR c.803delA (p.Asn268IlefsX17) 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 2e-05 in 246354 control chromosomes. c.803delA has been reported in the literature in individuals affected with Cystic Fibrosis (example, Orozco_2000, Wong_2001, Wang_2000, Schrijver_2008) as a relatively common CF causing allele identified in US Hispanics (Schrijver_2008). These data indicate that the variant is likely to be associated with disease. No experimental evidence demonstrating an impact on protein function were ascertained or evaluated in the scope of this classification. One clinical diagnostic laboratory and the CFTR2 database have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000047258	SCV002154271	pathogenic	Cystic fibrosis	2023-09-27	criteria provided, single submitter	clinical testing	This variant is also known as 935delA. This premature translational stop signal has been observed in individual(s) with cystic fibrosis (PMID: 10798368, 18456578, 22975760). This variant is present in population databases (rs121908772, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Asn268Ilefs*17) 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). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 48700).
Johns Hopkins Genomics, Johns Hopkins University	RCV000047258	SCV002570324	pathogenic	Cystic fibrosis	2022-09-06	criteria provided, single submitter	clinical testing	Disease-causing CFTR variant. See www.CFTR2.org for phenotype information.
Ambry Genetics	RCV000047258	SCV002677493	pathogenic	Cystic fibrosis	2024-09-24	criteria provided, single submitter	clinical testing	The c.803delA pathogenic mutation, located in coding exon 7 of the CFTR gene, results from a deletion of one nucleotide at nucleotide position 803, causing a translational frameshift with a predicted alternate stop codon (p.N268Ifs*17). This alteration was described in two individuals with a second CFTR alteration, failure to thrive, meconium ileus, elevated sweat chloride levels, and pancreatic insufficiency (Wang J et al. Mol. Genet. Metab., 2000 Aug;70:316-21). 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	RCV003473297	SCV004213303	pathogenic	Bronchiectasis with or without elevated sweat chloride 1	2024-03-29	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000790728	SCV004234590	pathogenic	not provided	2023-03-20	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV005031483	SCV005673299	pathogenic	Bronchiectasis with or without elevated sweat chloride 1; Cystic fibrosis; Hereditary pancreatitis; Congenital bilateral aplasia of vas deferens from CFTR mutation	2024-04-04	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001831714	SCV002078140	pathogenic	CFTR-related disorder	2017-03-17	no assertion criteria provided	clinical testing