ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.2354G>A (p.Arg785Gln) (rs141880790)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000695653 SCV000824165 uncertain significance Cystic fibrosis 2019-10-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 785 of the CFTR protein (p.Arg785Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs141880790, ExAC 0.01%). This variant has been reported in an individual affected with pancreatitis (PMID: 17003641). ClinVar contains an entry for this variant (Variation ID: 573871). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000757080 SCV000885181 uncertain significance not specified 2018-11-23 criteria provided, single submitter clinical testing The CFTR c.2354G>A; p.Arg785Gln variant (rs141880790) has been described in at least 2 individual with pancreatitis, but its association with disease is unclear (Keiles 2006, Ooi 2010). It is also observed in general population at an overall frequency of 0.003% (6/179874 alleles) in the Genome Aggregation Database. The arginine at codon 785 is weakly conserved and computational algorithms (PolyPhen-2, SIFT) predict that this variant is tolerated. Due to limited information regarding this variant, its clinical significance cannot be determined with certainty. References: Keiles S et al. Identification of CFTR, PRSS1, and SPINK1 mutations in 381 patients with pancreatitis. Pancreas. 2006 Oct;33(3):221-7. Ooi C et al. Genetic testing in pancreatitis. Gastroenterology. 2010 Jun;138(7):2202-6, 2206.e1.

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