ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.2502T>G (p.Phe834Leu) (rs200735475)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000542704 SCV000625737 uncertain significance Cystic fibrosis 2018-01-25 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with leucine at codon 834 of the CFTR protein (p.Phe834Leu). The phenylalanine residue is weakly conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is present in population databases (rs200735475, ExAC 0.1%). This variant has been reported in the compound heterozygous state in two individuals affected with chronic pancreatitis (PMID: 17003641). 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 leucine 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. In summary, this variant is a rare missense change that is not predicted to affect protein function, and is found in the population at an appreciable frequency. This variant is not anticipated to cause disease; however, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Integrated Genetics/Laboratory Corporation of America RCV000586636 SCV000696903 uncertain significance not provided 2017-06-26 criteria provided, single submitter clinical testing Variant summary: The CFTR c.2502T>G (p.Phe834Leu) variant involves the alteration of a non-conserved nucleotide, resulting in a missense change in the CFTR regulator domain (InterPro). 4/4 in silico tools predict a benign outcome for this variant. This variant was found in the large control database ExAC at a frequency of 0.0002558 (31/121184 control chromosomes), which does not exceed the estimated maximal expected allele frequency of a pathogenic CFTR variant (0.0129603). The variant has been found in CF and pancreatitis patients without supporting cosegregation data (Keiles_P2006; Soltysova_2017). Taken together, this variant is classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available.
Counsyl RCV000542704 SCV000796974 uncertain significance Cystic fibrosis 2018-01-05 criteria provided, single submitter clinical testing

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