Submissions for variant NM_000492.4(CFTR):c.3276C>G (p.Tyr1092Ter)

dbSNP: rs121908761

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR2	RCV000056380	SCV000087510	pathogenic	Cystic fibrosis	2017-03-17	reviewed by expert panel	research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000780122	SCV000917166	pathogenic	not specified	2018-09-07	criteria provided, single submitter	clinical testing	Variant summary: CFTR c.3276C>G (p.Tyr1092X) 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 (e.g., p.Glu1104X and p.Ala1146fsX2). The variant was absent in 245922 control chromosomes. c.3276C>G has been reported in the literature in multiple individuals affected with Cystic Fibrosis (Sosnay_2013). These data indicate that the variant is very likely to be associated with disease. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and both classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
CFTR-France	RCV001009514	SCV001169609	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
Myriad Genetics, Inc.	RCV000056380	SCV001194062	pathogenic	Cystic fibrosis	2019-12-09	criteria provided, single submitter	clinical testing	NM_000492.3(CFTR):c.3276C>G(Y1092*) is classified as pathogenic in the context of cystic fibrosis and is associated with classic disease. Sources cited for classification include the following: PMID 16049310 and 23974870. Classification of NM_000492.3(CFTR):c.3276C>G(Y1092*) 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000056380	SCV004295559	pathogenic	Cystic fibrosis	2023-04-27	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: 7211). This premature translational stop signal has been observed in individual(s) with clinical features of CFTR-related conditions (PMID: 23974870, 28546993). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr1092*) 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).
Natera, Inc.	RCV001831551	SCV002083622	pathogenic	CFTR-related disorder	2017-03-17	no assertion criteria provided	clinical testing