ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6757C>T (p.Leu2253Phe)

gnomAD frequency: 0.00001  dbSNP: rs786203252
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000776788 SCV000912439 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-26 criteria provided, single submitter clinical testing This missense variant replaces leucine with phenylalanine at codon 2253 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with APC-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae RCV003653313 SCV001220168 uncertain significance Familial adenomatous polyposis 1 2020-10-01 criteria provided, single submitter clinical testing 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. 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 phenylalanine 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. This variant has not been reported in the literature in individuals with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 630789). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with phenylalanine at codon 2253 of the APC protein (p.Leu2253Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine.
Ambry Genetics RCV000776788 SCV002666453 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-29 criteria provided, single submitter clinical testing The p.L2253F variant (also known as c.6757C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 6757. The leucine at codon 2253 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.