Submissions for variant NM_000492.4(CFTR):c.3293G>A (p.Trp1098Ter)

dbSNP: rs397508532

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR2	RCV000046855	SCV000245949	pathogenic	Cystic fibrosis	2017-03-17	reviewed by expert panel	research
CFTR-France	RCV001009509	SCV001169604	pathogenic	Cystic fibrosis; CFTR-related disorder	2018-01-29	criteria provided, single submitter	curation	the variant causes a phenotype but regarding our data, we can't formally attribute it to CF, CFTR-RD or both
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000046855	SCV001448435	pathogenic	Cystic fibrosis	2020-11-11	criteria provided, single submitter	clinical testing	Variant summary: CFTR c.3293G>A (p.Trp1098X) 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 251088 control chromosomes. c.3293G>A has been reported in the literature in individuals affected with Cystic Fibrosis (e.g. Chillon_1994, Claustres_2000, McCague_2019, Ruiz-Cabezas_2019). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) have cited the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Ambry Genetics	RCV000046855	SCV002611686	pathogenic	Cystic fibrosis	2015-02-03	criteria provided, single submitter	clinical testing	The p.W1098* pathogenic mutation (also known as c.3293G>A and p.W1098X), located in coding exon 20 of the CFTR gene, results from a G to A substitution at nucleotide position 3293. This changes the amino acid from a tryptophan to a stop codon within coding exon 20. This pathogenic mutation was first reported in the literature as identified in an individual with cystic fibrosis and a sweat chloride >80mmol/L; however, specific clinical information or the presence of a second mutation was not provided (Chillón M et al. Hum Genet. 1994;93(4):447-51). 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).
Labcorp Genetics (formerly Invitae), Labcorp	RCV000046855	SCV004295561	pathogenic	Cystic fibrosis	2024-10-13	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Trp1098*) 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: 7513293, 30763667). This variant is also known as W1098*. ClinVar contains an entry for this variant (Variation ID: 53708). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV004566877	SCV005057414	pathogenic	Bronchiectasis with or without elevated sweat chloride 1	2024-03-20	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001831771	SCV002083626	pathogenic	CFTR-related disorder	2017-03-17	no assertion criteria provided	clinical testing