ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1205G>A (p.Arg402His) (rs878853416)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000230439 SCV000282690 uncertain significance Familial adenomatous polyposis 1 2018-12-27 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 402 of the APC protein (p.Arg402His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 236557). 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: "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.
GeneDx RCV000484776 SCV000566728 uncertain significance not provided 2018-03-15 criteria provided, single submitter clinical testing This variant is denoted APC c.1205G>A at the cDNA level, p.Arg402His (R402H) at the protein level, and results in the change of an Arginine to a Histidine (CGT>CAT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Arg402His was not observed 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 Arg402His is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV001010300 SCV001170475 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-22 criteria provided, single submitter clinical testing In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Insufficient evidence;Rarity in general population databases (dbsnp, esp, 1000 genomes)

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