ClinVar Miner

Submissions for variant NM_000038.6(APC):c.2503T>C (p.Ser835Pro) (rs748302469)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483161 SCV000566885 uncertain significance not provided 2018-05-07 criteria provided, single submitter clinical testing This variant is denoted APC c.2503T>C at the cDNA level, p.Ser835Pro (S835P) at the protein level, and results in the change of a Serine to a Proline (TCT>CCT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Ser835Pro was not observed at a significant allele frequency in large population cohorts (Lek 2016). APC Ser835Pro 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 information, it is unclear whether APC Ser835Pro is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000646289 SCV000768057 uncertain significance Familial adenomatous polyposis 1 2017-09-14 criteria provided, single submitter clinical testing This sequence change replaces serine with proline at codon 835 of the APC protein (p.Ser835Pro). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and proline. This variant is present in population databases (rs748302469, 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: 419216). 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: "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.
PreventionGenetics,PreventionGenetics RCV000483161 SCV000805382 uncertain significance not provided 2018-01-17 criteria provided, single submitter clinical testing
Color RCV000771555 SCV000904119 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-28 criteria provided, single submitter clinical testing

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