ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7174C>A (p.Pro2392Thr) (rs730881257)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159568 SCV000209543 uncertain significance not provided 2018-10-05 criteria provided, single submitter clinical testing This variant is denoted APC c.7174C>A at the cDNA level, p.Pro2392Thr (P2392T) at the protein level, and results in the change of a Proline to a Threonine (CCA>ACA). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. APC Pro2392Thr 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 a deleterious effect. Based on currently available evidence, it is unclear whether APC Pro2392Thr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000219951 SCV000273674 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Counsyl RCV000409928 SCV000489561 uncertain significance Familial adenomatous polyposis 1 2016-10-27 criteria provided, single submitter clinical testing
Invitae RCV000409928 SCV000552493 uncertain significance Familial adenomatous polyposis 1 2018-12-19 criteria provided, single submitter clinical testing This sequence change replaces proline with threonine at codon 2392 of the APC protein (p.Pro2392Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine. This variant is present in population databases (rs730881257, ExAC 0.003%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 181816). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Color RCV000219951 SCV000681852 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-17 criteria provided, single submitter clinical testing

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