ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1279C>A (p.His427Asn) (rs587779781)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766425 SCV000148977 uncertain significance not provided 2018-12-10 criteria provided, single submitter clinical testing This variant is denoted APC c.1279C>A at the cDNA level, p.His427Asn (H427N) at the protein level, and results in the change of a Histidine to an Asparagine (CAT>AAT). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. APC His427Asn was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether APC His427Asn is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000115068 SCV000600040 uncertain significance not specified 2017-01-26 criteria provided, single submitter clinical testing
Invitae RCV000536980 SCV000647167 uncertain significance Familial adenomatous polyposis 1 2018-05-12 criteria provided, single submitter clinical testing This sequence change replaces histidine with asparagine at codon 427 of the APC protein (p.His427Asn). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and asparagine. This variant is present in population databases (rs587779781, ExAC 0.002%) but has not been reported in the literature in individuals with an APC-related disease. ClinVar contains an entry for this variant (Variation ID: 127276). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneKor MSA RCV000708636 SCV000821807 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing

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