ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7105C>T (p.Pro2369Ser) (rs377308875)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000220467 SCV000277218 uncertain significance Hereditary cancer-predisposing syndrome 2018-02-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient evidence
Invitae RCV000231080 SCV000282813 uncertain significance Familial adenomatous polyposis 1 2018-12-03 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 2369 of the APC protein (p.Pro2369Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs377308875, ExAC 0.005%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 232940). 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 RCV000236554 SCV000292464 uncertain significance not provided 2018-09-10 criteria provided, single submitter clinical testing This variant is denoted APC c.7105C>T at the cDNA level, p.Pro2369Ser (P2369S) at the protein level, and results in the change of a Proline to a Serine (CCA>TCA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Pro2369Ser was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in within 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 Pro2369Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000220467 SCV000681848 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-14 criteria provided, single submitter clinical testing

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