Submissions for variant NM_000492.4(CFTR):c.2374C>T (p.Arg792Ter)

dbSNP: rs145449046

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR2	RCV000046586	SCV000245893	pathogenic	Cystic fibrosis	2017-03-17	reviewed by expert panel	research
Counsyl	RCV000046586	SCV000792990	pathogenic	Cystic fibrosis	2017-07-25	criteria provided, single submitter	clinical testing
Mendelics	RCV000046586	SCV000886261	pathogenic	Cystic fibrosis	2018-11-05	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000780127	SCV000917171	pathogenic	not specified	2018-02-08	criteria provided, single submitter	clinical testing	Variant summary: CFTR c.2374C>T (p.Arg792X) 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 (eg. c.2491G>T, p.Glu831X; c.2551C>T, p.Arg851X; c.2554dupT, p.Tyr852fsX44). The variant was absent in 110418 control chromosomes (ExAC). The variant has been reported in CF patients in the literature in trans with pathogenic CFTR variants (Claustres_2000, des Georges_2004, Sanchez_2016, Shen_2016, Tian_2016, and Filleron_2011). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014, which classified it as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics	RCV001004475	SCV001163520	pathogenic	Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation		criteria provided, single submitter	clinical testing
CFTR-France	RCV000046586	SCV001169555	pathogenic	Cystic fibrosis	2018-01-29	criteria provided, single submitter	curation
Johns Hopkins Genomics, Johns Hopkins University	RCV000046586	SCV001371810	pathogenic	Cystic fibrosis	2020-01-27	criteria provided, single submitter	clinical testing	Disease-causing CFTR variant. See www.CFTR2.org for phenotype information.
Invitae	RCV000046586	SCV001579718	pathogenic	Cystic fibrosis	2023-11-25	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg792*) 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 present in population databases (rs145449046, gnomAD 0.007%). This premature translational stop signal has been observed in individuals with cystic fibrosis (PMID: 7691344, 27081564, 28603918). ClinVar contains an entry for this variant (Variation ID: 53483). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV000046586	SCV002736407	pathogenic	Cystic fibrosis	2023-03-10	criteria provided, single submitter	clinical testing	The p.R792* pathogenic mutation (also known as c.2374C>T), located in coding exon 14 of the CFTR gene, results from a C to T substitution at nucleotide position 2374. This changes the amino acid from an arginine to a stop codon within coding exon 14. This mutation was first detected in an individual with cystic fibrosis; however, the presence of a second CFTR variant was not reported (Claustres M et al. Hum Mol Genet, 1993 Aug;2:1209-13). This variant has been reported in multiple individuals with an elevated sweat chloride level in The Clinical and Functional TRanslation of CFTR (CFTR2) database (available at http://cftr2.org. Accessed 3/9/2023). 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.
Natera, Inc.	RCV001826636	SCV002080737	pathogenic	CFTR-related disorders	2017-03-17	no assertion criteria provided	clinical testing