ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3299C>T (p.Ser1100Phe) (rs863224541)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000195761 SCV000254005 uncertain significance Familial adenomatous polyposis 1 2018-10-29 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 1100 of the APC protein (p.Ser1100Phe). 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 been reported in an individual with suspected Lynch syndrome (PMID: 25980754). ClinVar contains an entry for this variant (Variation ID: 216159). 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: "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 RCV000235272 SCV000292912 uncertain significance not provided 2018-08-13 criteria provided, single submitter clinical testing This variant is denoted APC c.3299C>T at the cDNA level, p.Ser1100Phe (S1100F) at the protein level, and results in the change of a Serine to a Phenylalanine (TCT>TTT). This variant was observed in at least one individual with a personal history of a Lynch syndrome-associated cancer and/or polyps (Yurgelun 2015). APC Ser1100Phe was not observed at a significant allele frequency in large population cohorts (Lek 2016). APC Ser1100Phe is located in the 15 amino acid repeat beta-catenin binding domain (Azzopardi 2008). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether APC Ser1100Phe is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000574827 SCV000667424 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-15 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000574827 SCV000681589 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-23 criteria provided, single submitter clinical testing

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