ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5189C>T (p.Ser1730Phe) (rs864622256)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000204727 SCV000259864 uncertain significance Familial adenomatous polyposis 1 2018-10-21 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 1730 of the APC protein (p.Ser1730Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is not present in population databases and has not been reported in the germline of affected patients in the literature. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000216423 SCV000276985 uncertain significance Hereditary cancer-predisposing syndrome 2017-07-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
GeneDx RCV000236704 SCV000293120 uncertain significance not provided 2018-08-09 criteria provided, single submitter clinical testing This variant is denoted APC c.5189C>T at the cDNA level, p.Ser1730Phe (S1730F) 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 reportedly healthy individual (Azzopardi 2008). APC Ser1730Phe was not observed at a significant allele frequency in large population cohorts (Lek 2016). APC Ser1730Phe is located within the Beta-catenin down-regulating domain and the SAMP repeats/axin 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 information, it is unclear whether APC Ser1730Phe is pathogenic or benign. We consider it to be a variant of uncertain significance.
Color RCV000216423 SCV000681713 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-18 criteria provided, single submitter clinical testing

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