Submissions for variant NM_000492.4(CFTR):c.38C>T (p.Ser13Phe)

dbSNP: rs397508635

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR2	RCV000577001	SCV000924231	pathogenic	Cystic fibrosis	2018-08-31	reviewed by expert panel	research
Counsyl	RCV000577001	SCV000800113	uncertain significance	Cystic fibrosis	2018-05-22	criteria provided, single submitter	clinical testing
Mendelics	RCV000577001	SCV000886335	pathogenic	Cystic fibrosis	2018-11-05	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759040	SCV000888093	likely pathogenic	not provided	2021-04-23	criteria provided, single submitter	clinical testing	This variant has been reported in individuals affected with cystic fibrosis, and in some of those individuals other pathogenic CFTR variants were also identified (PMID: 31245908 (2019), 27086061 (2016), 23405520 (2012), 11158459 (2001), 9554753 (1998)). A functional study has reported that this variant is detrimental to CFTR processing, stability, and surface expression. However the full effect on CFTR function is unknown (PMID: 17235394 (2007). The frequency of this variant in the general population is consistent with pathogenicity. Occurs in 3 or more cases with a lone recessive pathogenic/likely pathogenic variant in the same gene, however only 1-2 cases have phenotype known to be consistent with disease. Based on the available information, the variant is classified as likely pathogenic.
Baylor Genetics	RCV001004226	SCV001163102	likely pathogenic	Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000577001	SCV002235727	pathogenic	Cystic fibrosis	2023-10-22	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 13 of the CFTR protein (p.Ser13Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with cystic fibrosis (PMID: 9554753, 11158459, 27086061, 31245908). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 53845). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CFTR protein function. Experimental studies have shown that this missense change affects CFTR function (PMID: 17235394, 20351101). For these reasons, this variant has been classified as Pathogenic.
CFTR-France	RCV000577001	SCV002573598	pathogenic	Cystic fibrosis	2020-03-26	criteria provided, single submitter	curation
Baylor Genetics	RCV003474596	SCV004213571	pathogenic	Bronchiectasis with or without elevated sweat chloride 1	2023-02-04	criteria provided, single submitter	clinical testing
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000577001	SCV000679454	not provided	Cystic fibrosis		no assertion provided	literature only
Natera, Inc.	RCV000577001	SCV001464065	pathogenic	Cystic fibrosis	2020-09-16	no assertion criteria provided	clinical testing