ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7143A>C (p.Gln2381His) (rs756153152)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000203991 SCV000260764 uncertain significance Familial adenomatous polyposis 1 2015-09-20 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 2381 of the APC protein (p.Gln2381His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine. This variant is present in population databases (ExAC 0.02%) but has not been reported in the literature. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this is a rare missense change with uncertain impact on protein function. There is no indication that this variant causes disease, but the evidence is insufficient at this time to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000236701 SCV000294102 uncertain significance not provided 2018-12-13 criteria provided, single submitter clinical testing This variant is denoted APC c.7143A>C at the cDNA level, p.Gln2381His (Q2381H) 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 Gln2381His was not observed at a significant allele 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 evidence, it is unclear whether APC Gln2381His is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000568621 SCV000667635 uncertain significance Hereditary cancer-predisposing syndrome 2016-08-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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