Submissions for variant NM_000492.4(CFTR):c.1585-8G>A

dbSNP: rs193922503

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR2	RCV000029481	SCV000071567	pathogenic	Cystic fibrosis	2017-03-17	reviewed by expert panel	research
Mendelics	RCV000029481	SCV000886240	pathogenic	Cystic fibrosis	2018-11-05	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759756	SCV000889292	pathogenic	not provided	2016-08-31	criteria provided, single submitter	clinical testing
CFTR-France	RCV000029481	SCV001169470	pathogenic	Cystic fibrosis	2018-01-29	criteria provided, single submitter	curation
Labcorp Genetics (formerly Invitae), Labcorp	RCV000029481	SCV001586669	pathogenic	Cystic fibrosis	2023-09-28	criteria provided, single submitter	clinical testing	This sequence change falls in intron 11 of the CFTR gene. It does not directly change the encoded amino acid sequence of the CFTR protein. For these reasons, this variant has been classified as Pathogenic. Studies have shown that this variant alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 23381846, 25066652). ClinVar contains an entry for this variant (Variation ID: 35828). This variant is also known as c.1717-8G>A. This variant has been observed in individuals with cystic fibrosis (PMID: 7512860, 23974870). This variant is not present in population databases (gnomAD no frequency).
Mayo Clinic Laboratories, Mayo Clinic	RCV000759756	SCV001713420	pathogenic	not provided	2020-05-01	criteria provided, single submitter	clinical testing	PS3, PS4_Moderate, PM2, PP1, PP3, PP4, PP5
Ambry Genetics	RCV000029481	SCV002705652	pathogenic	Cystic fibrosis	2023-07-19	criteria provided, single submitter	clinical testing	The c.1585-8G>A intronic pathogenic mutation (also known as c.1717-8G>A) results from a G to A substitution 8 nucleotides upstream from coding exon 12 in the CFTR gene. This mutation was first identified in the heterozygous state in two cousins with recurrent pulmonary infections, pancreatic insufficiency, and positive sweat chloride tests (Savov A et al. Hum. Molec. Genet. 1994;3(1):57-60); one cousin also carried the p.F508del mutation on the opposite allele. This alteration has also been reported as a rare mutation identified in Spanish cystic fibrosis patients (Alonso MJ et al. Ann Hum Genet 2007;71(Pt2):194-201). Functional in vitro studies found that cells carrying this pathogenic mutation did not produce correctly spliced RNA or mature CFTR protein (Sosnay PR et al. Nat Genet. 2013;45(10):1160-7). The c.1585-8G>A mutation produces an RNA transcript that includes the six last nucleotides of intron 11 (TAATAG) at the 5' end of exon 12, leading to the in-frame inclusion of two consecutive premature termination codons (Raynal C et al. Hum Mutat 2013;34(5):774-84). This mutation is typically associated with elevated sweat chloride levels and pancreatic insufficiency (Sosnay PR et al. Nat Genet. 2013;45(10):1160-7). In addition, this variant has been detected in the homozygous state by our laboratory. Based on the supporting evidence, c.1585-8G>A is interpreted as a disease-causing mutation.
Baylor Genetics	RCV003473127	SCV004213537	pathogenic	Bronchiectasis with or without elevated sweat chloride 1	2024-03-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000029481	SCV000052131	pathogenic	Cystic fibrosis	2015-04-03	no assertion criteria provided	clinical testing
Counsyl	RCV000029481	SCV000798065	pathogenic	Cystic fibrosis	2018-02-21	no assertion criteria provided	clinical testing
Natera, Inc.	RCV001826511	SCV002080620	pathogenic	CFTR-related disorder	2017-03-17	no assertion criteria provided	clinical testing