Submissions for variant NM_000492.4(CFTR):c.1882G>C (p.Gly628Arg)

dbSNP: rs397508316

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR2	RCV000577206	SCV000924273	pathogenic	Cystic fibrosis	2019-03-11	reviewed by expert panel	research
Eurofins Ntd Llc (ga)	RCV000730837	SCV000858601	likely pathogenic	not provided	2017-12-22	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000577206	SCV002246033	pathogenic	Cystic fibrosis	2023-05-01	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 628 of the CFTR protein (p.Gly628Arg). This missense change has been observed in individuals with CFTR-related conditions (PMID: 10923036, 27022295). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects CFTR function (PMID: 20435887). 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. ClinVar contains an entry for this variant (Variation ID: 53409).
Ambry Genetics	RCV000577206	SCV005035934	likely pathogenic	Cystic fibrosis	2023-02-10	criteria provided, single submitter	clinical testing	The p.G628R variant (also known as c.1882G>C), located in coding exon 14 of the CFTR gene, results from a G to C substitution at nucleotide position 1882. The glycine at codon 628 is replaced by arginine, an amino acid with dissimilar properties. This alteration has been identified in an individual with a clinical diagnosis of cystic fibrosis (Cuppens H et al. Genomics, 1993 Dec;18:693-7). 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 02/10/2023). This variant has 0.8% of wild type function in The Clinical and Functional TRanslation of CFTR (CFTR2) database (available at http://cftr2.org. Accessed 02/10/2023).This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000577206	SCV005075791	pathogenic	Cystic fibrosis	2024-04-03	criteria provided, single submitter	clinical testing	Variant summary: CFTR c.1882G>C (p.Gly628Arg) results in a non-conservative amino acid change located in the ABC transporter-like, ATP-binding domain (IPR003439) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 244320 control chromosomes. c.1882G>C has been reported in the literature in multiple compound heterozygous individuals affected with Cystic Fibrosis or CBAVD (e.g. Geurts_2020, Claustres_2000). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, showing largely reduced current density in CFTR channels (e.g. Billet_2010). The following publications have been ascertained in the context of this evaluation (PMID: 20435887, 10923036, 32084388). ClinVar contains an entry for this variant (Variation ID: 53409). Based on the evidence outlined above, the variant was classified as pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV005031495	SCV005673344	likely pathogenic	Bronchiectasis with or without elevated sweat chloride 1; Cystic fibrosis; Hereditary pancreatitis; Congenital bilateral aplasia of vas deferens from CFTR mutation	2024-04-03	criteria provided, single submitter	clinical testing
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000577206	SCV000678973	not provided	Cystic fibrosis		no assertion provided	literature only
Natera, Inc.	RCV001831739	SCV002080682	pathogenic	CFTR-related disorder	2017-09-01	no assertion criteria provided	clinical testing