ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6577A>G (p.Lys2193Glu) (rs1060503343)

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
Invitae RCV000470220 SCV000552697 uncertain significance Familial adenomatous polyposis 1 2016-05-27 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 2193 of the APC protein (p.Lys2193Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a APC-related disease. 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: "Possibly Damaging"; Align-GVGD: "Class C15"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
GeneDx RCV000522688 SCV000620025 uncertain significance not provided 2018-06-28 criteria provided, single submitter clinical testing The K2193E variant in the APC gene has not, to our knowledge, been published in the literature as pathogenic or benign. This variant was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Lysine and Glutamic Acid differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. This substitution occurs at a position that is conserved across species and in silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, we consider K2193E to be a variant of uncertain significance.
Ambry Genetics RCV000569629 SCV000667509 uncertain significance Hereditary cancer-predisposing syndrome 2016-02-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)

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.