ClinVar

Description

The CFTR c.508C>T; p.Arg170Cys variant (rs578029902) is reported in the literature in the heterozygous state individuals affected with CFTR-related disorders (Casals 2004, Coste 2004, de Cid 2010, Sharma 2014), and in one individual with alcohol-related pancreatitis who also carries a common pathogenic CFTR variant (Bernardino 2003). This variant is reported in ClinVar (Variation ID: 455782), and is found in the general population with an overall allele frequency of 0.005% (13/250410 alleles) in the Genome Aggregation Database. The arginine at residue 170 is highly conserved, and computational algorithms (PolyPhen-2, SIFT) predict that this variant is deleterious. Additionally, other variants at this codon (c.509G>A; p.Arg170His, c.508C>G; p.Arg170Gly) have been reported in individuals with CFTR-related diseases (Palermo 2016, see link to cystic fibrosis mutation database). Based on available information, the p.Arg170Cys variant is not expected to cause classic cystic fibrosis, however, it remains uncertain whether it may contribute to the clinical phenotype in individuals with milder CFTR-related disease (e.g., an isolated presentation of pancreatitis, congenital bilateral absence of the vas deferens, or mild lung disease). References: Link to cystic fibrosis mutation database: http://genet.sickkids.on.ca/cftr/Home.html Bernardino AL et al. CFTR, PRSS1 and SPINK1 mutations in the development of pancreatitis in Brazilian patients. JOP. 2003 Sep;4(5):169-77. Casals T et al. Different CFTR mutational spectrum in alcoholic and idiopathic chronic pancreatitis? Pancreas. 2004 May;28(4):374-9. Coste A et al. Atypical sinusitis in adults must lead to looking for cystic fibrosis and primary ciliary dyskinesia. Laryngoscope. 2004 May;114(5):839-43. de Cid R et al. Independent contribution of common CFTR variants to chronic pancreatitis. Pancreas. 2010 Mar;39(2):209-15. Palermo JJ et al. Genophenotypic Analysis of Pediatric Patients With Acute Recurrent and Chronic Pancreatitis. Pancreas. 2016 Oct;45(9):1347-52. Sharma H et al. Heterogeneous spectrum of mutations in CFTR gene from Indian patients with congenital absence of the vas deferens and their association with cystic fibrosis genetic modifiers. Mol Hum Reprod. 2014 Sep;20(9):827-35.