ClinVar Miner

Submissions for variant NM_000038.5(APC):c.4376C>G (p.Thr1459Ser) (rs756048549)

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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 RCV000214073 SCV000274036 likely benign Hereditary cancer-predisposing syndrome 2017-06-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Co-occurence with mutation in same gene (phase unknown)
Color RCV000214073 SCV000906434 likely benign Hereditary cancer-predisposing syndrome 2016-03-21 criteria provided, single submitter clinical testing
Counsyl RCV000461981 SCV000784763 uncertain significance Familial adenomatous polyposis 1 2017-11-13 criteria provided, single submitter clinical testing
Invitae RCV000461981 SCV000552444 uncertain significance Familial adenomatous polyposis 1 2018-03-20 criteria provided, single submitter clinical testing This sequence change replaces threonine with serine at codon 1459 of the APC protein (p.Thr1459Ser). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and serine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 230474). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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