ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1440A>C (p.Gln480His) (rs863224537)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236105 SCV000293119 uncertain significance not provided 2018-08-02 criteria provided, single submitter clinical testing This variant is denoted APC c.1440A>C at the cDNA level, p.Gln480His (Q480H) at the protein level, and results in the change of a Glutamine to a Histidine (CAA>CAC). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. APC Gln480His was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the armadillo region (Azzopardi 2008). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether APC Gln480His is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000504394 SCV000591073 pathogenic Familial adenomatous polyposis 2015-11-20 criteria provided, single submitter clinical testing
Invitae RCV000705339 SCV000834331 uncertain significance Familial adenomatous polyposis 1 2018-06-28 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 480 of the APC protein (p.Gln480His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Universal Mutation Database (PMID: 10612827). ClinVar contains an entry for this variant (Variation ID: 245917). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; 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.

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