ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6117G>T (p.Leu2039Phe) (rs372418435)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163274 SCV000213802 uncertain significance Hereditary cancer-predisposing syndrome 2017-04-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000232978 SCV000282791 uncertain significance Familial adenomatous polyposis 1 2018-12-27 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 2039 of the APC protein (p.Leu2039Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is present in population databases (rs372418435, ExAC 0.003%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 184130). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
GeneDx RCV000656748 SCV000292462 uncertain significance not provided 2017-12-06 criteria provided, single submitter clinical testing This variant is denoted APC c.6117G>T at the cDNA level, p.Leu2039Phe (L2039F) at the protein level, and results in the change of a Leucine to a Phenylalanine (TTG>TTT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Leu2039Phe was not observed at a significant allele frequency in large population cohorts (Lek 2016). Since Leucine and Phenylalanine share similar properties, this is considered a conservative amino acid substitution. APC Leu2039Phe is located in the SAMP repeats and axin binding domain (Azzopardi 2008). In silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Based on currently available evidence, it is unclear whether APC Leu2039Phe is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Counsyl RCV000232978 SCV000489035 uncertain significance Familial adenomatous polyposis 1 2016-08-10 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000236184 SCV000591195 uncertain significance not specified 2015-09-01 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000236184 SCV000600123 uncertain significance not specified 2017-03-24 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000236184 SCV000602534 uncertain significance not specified 2017-02-10 criteria provided, single submitter clinical testing
Color RCV000163274 SCV000681781 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-06 criteria provided, single submitter clinical testing

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.