ClinVar Miner

Submissions for variant NM_000038.6(APC):c.2642C>T (p.Ser881Phe) (rs535344579)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000204328 SCV000259303 uncertain significance Familial adenomatous polyposis 1 2018-05-29 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 881 of the APC protein (p.Ser881Phe). The serine residue is moderately conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature as a germline variant in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 219437). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Benign"; 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 RCV000478187 SCV000572228 uncertain significance not provided 2018-03-29 criteria provided, single submitter clinical testing This variant is denoted APC c.2642C>T at the cDNA level, p.Ser881Phe (S881F) at the protein level, and results in the change of a Serine to a Phenylalanine (TCC>TTC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Ser881Phe 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 a deleterious effect. Based on currently available evidence, it is unclear whether APC Ser881Phe is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000565056 SCV000675876 uncertain significance Hereditary cancer-predisposing syndrome 2016-01-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Mendelics RCV000204328 SCV000838094 uncertain significance Familial adenomatous polyposis 1 2018-07-02 criteria provided, single submitter clinical testing
Color RCV000565056 SCV000904121 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-09 criteria provided, single submitter clinical testing

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