ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6694C>G (p.His2232Asp) (rs730881256)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000656749 SCV000209540 uncertain significance not provided 2018-01-23 criteria provided, single submitter clinical testing This variant is denoted APC c.6694C>G at the cDNA level, p.His2232Asp (H2232D) at the protein level, and results in the change of a Histidine to an Aspartic Acid (CAT>GAT). This variant was observed in a non-FAP/non-MAP patient with colorectal adenomas (Azzopardi 2008). APC His2232Asp was not observed at a significant allele frequency in large population cohorts (Lek 2016). APC His2232Asp is located in the basic domain (Azzopardi 2008). In-silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether APC His2232Asp is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000204441 SCV000259792 uncertain significance Familial adenomatous polyposis 1 2018-11-21 criteria provided, single submitter clinical testing This sequence change replaces histidine with aspartic acid at codon 2232 of the APC protein (p.His2232Asp). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and aspartic acid. This variant is present in population databases (rs730881256, ExAC 0.01%). This variant has been reported in an individual affected with colorectal adenomas (PMID: 18199528). ClinVar contains an entry for this variant (Variation ID: 181815). 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 C15"). 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.
Ambry Genetics RCV000216441 SCV000273988 uncertain significance Hereditary cancer-predisposing syndrome 2018-01-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Counsyl RCV000204441 SCV000489562 uncertain significance Familial adenomatous polyposis 1 2016-10-27 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000159567 SCV000600136 uncertain significance not specified 2017-06-04 criteria provided, single submitter clinical testing
Color RCV000216441 SCV000681818 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-14 criteria provided, single submitter clinical testing

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