ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3926A>G (p.Glu1309Gly) (rs775060363)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000464698 SCV000552699 uncertain significance Familial adenomatous polyposis 1 2016-05-13 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glycine at codon 1309 of the APC protein (p.Glu1309Gly). The glutamic acid residue is moderately conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in a single family affected with suspected familial juvenile polyposis coli (PMID: 9382065). This variant was observed in one affected individual, but were absent in the two other affected individuals. 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: "Benign"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. It is not expected to cause disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000479602 SCV000568278 uncertain significance not provided 2016-05-02 criteria provided, single submitter clinical testing This variant is denoted APC c.3926A>G at the cDNA level, p.Glu1309Gly (E1309G) at the protein level, and results in the change of a Glutamic Acid to a Glycine (GAA>GGA). This variant was observed in a patient with juvenile polyposis (Kim 1997). APC Glu1309Gly 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 Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. APC Glu1309Gly occurs at a position that is not conserved and is located in the 20 amino acid repeat beta-catenin down-regulating domain and within the region responsible for down-regulation through a process mediated by direct ubiquitination (Azzopardi 2008, UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether APC Glu1309Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000581098 SCV000681640 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-17 criteria provided, single submitter clinical testing

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