ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7018A>C (p.Asn2340His) (rs748940586)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485956 SCV000565844 uncertain significance not provided 2018-07-25 criteria provided, single submitter clinical testing This variant is denoted APC c.7018A>C at the cDNA level, p.Asn2340His (N2340H) at the protein level, and results in the change of an Asparagine to a Histidine (AAC>CAC). This variant was observed in at least one individual with a personal and family history of colon cancer (Chubb 2015). APC Asn2340His was not observed at a significant frequency in large population cohorts (Lek 2016). This variant is located in the Basic 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 information, it is unclear whether APC Asn2340His is pathogenic or benign. We consider it to be a variant of uncertain significance.
Color RCV000582404 SCV000687107 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-11 criteria provided, single submitter clinical testing
Invitae RCV000646407 SCV000768176 uncertain significance Familial adenomatous polyposis 1 2018-12-27 criteria provided, single submitter clinical testing This sequence change replaces asparagine with histidine at codon 2340 of the APC protein (p.Asn2340His). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and histidine. This variant is present in population databases (rs748940586, ExAC 0.002%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 418637). 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: "Probably 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.

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