ClinVar Miner

Submissions for variant NM_000038.6(APC):c.8107A>G (p.Lys2703Glu) (rs730881270)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159581 SCV000209557 uncertain significance not provided 2018-02-22 criteria provided, single submitter clinical testing This variant is denoted APC c.8107A>G at the cDNA level, p.Lys2703Glu (K2703E) at the protein level, and results in the change of a Lysine to a Glutamic Acid (AAA>GAA). This variant has been reported in an individual with breast cancer and in another individual with an unspecified advanced cancer (Li 2017, Mandelker 2017). APC Lys2703Glu was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the EB1 binding domain (Azzopardi 2008). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether APC Lys2703Glu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Illumina Clinical Services Laboratory,Illumina RCV000322812 SCV000452055 uncertain significance APC-Associated Polyposis Disorders 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000525703 SCV000647753 uncertain significance Familial adenomatous polyposis 1 2019-01-02 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 2703 of the APC protein (p.Lys2703Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is present in population databases (rs730881270, 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: 181829). 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 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.
Ambry Genetics RCV000575937 SCV000675858 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000575937 SCV000681911 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-10 criteria provided, single submitter clinical testing
Clinical Genomics Lab,St. Jude Children's Research Hospital RCV000761026 SCV000890941 uncertain significance T Lymphoblastic Leukemia/Lymphoma 2016-03-03 no assertion criteria provided clinical testing

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