ClinVar Miner

Submissions for variant NM_000038.6(APC):c.212G>A (p.Arg71His) (rs750503329)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000474741 SCV000552603 uncertain significance Familial adenomatous polyposis 1 2018-11-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 71 of the APC protein (p.Arg71His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs750503329, ExAC 0.02%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 411444). 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.
GeneDx RCV000479660 SCV000569440 uncertain significance not provided 2018-04-10 criteria provided, single submitter clinical testing This variant is denoted APC c.212G>A at the cDNA level, p.Arg71His (R71H) 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 Arg71His 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 that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether APC Arg71His is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000571928 SCV000667392 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000571928 SCV000681504 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-08 criteria provided, single submitter clinical testing

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