Submissions for variant NM_000492.4(CFTR):c.1301_1307del (p.Ser434fs)

dbSNP: rs397508186

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR2	RCV000785637	SCV000924256	pathogenic	Cystic fibrosis	2017-12-08	reviewed by expert panel	research
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759749	SCV000889279	pathogenic	not provided	2018-05-23	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000785637	SCV001584170	pathogenic	Cystic fibrosis	2023-05-19	criteria provided, single submitter	clinical testing	Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 53225). This sequence change creates a premature translational stop signal (p.Ser434Leufs*6) 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 clinical features of cystic fibrosis (PMID: 15858154, 23974870). This variant is also known as 1429del7 or 1433delCACTTCT.
Mayo Clinic Laboratories, Mayo Clinic	RCV000759749	SCV001714233	pathogenic	not provided	2020-07-10	criteria provided, single submitter	clinical testing	PVS1, PM2, PP5
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000785637	SCV004241247	pathogenic	Cystic fibrosis	2023-12-18	criteria provided, single submitter	clinical testing	Variant summary: CFTR c.1301_1307delCACTTCT (p.Ser434LeufsX6) 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. Variants downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 245594 control chromosomes. c.1301_1307delCACTTCT has been reported in the literature in individuals affected with Cystic Fibrosis (eg. Schrijver_2005). Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Natera, Inc.	RCV000785637	SCV001456067	pathogenic	Cystic fibrosis	2020-09-16	no assertion criteria provided	clinical testing