ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3289G>A (p.Glu1097Lys) (rs1060503312)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000472254 SCV000552611 uncertain significance Familial adenomatous polyposis 1 2016-06-12 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 1097 of the APC protein (p.Glu1097Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000481132 SCV000570079 uncertain significance not provided 2016-04-25 criteria provided, single submitter clinical testing This variant is denoted APC c.3289G>A at the cDNA level, p.Glu1097Lys (E1097K) at the protein level, and results in the change of a Glutamic Acid to a Lysine (GAA>AAA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Glu1097Lys was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Glutamic Acid and Lysine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. APC Glu1097Lys occurs at a position that is conserved across species and is located within the 15-amino acid repeat Beta-catenin binding domain (Azzopardi 2008). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether APC Glu1097Lys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000569515 SCV000667652 uncertain significance Hereditary cancer-predisposing syndrome 2017-04-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence,In silico models in agreement (benign)

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