Submissions for variant NM_000038.6(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)
Invitae	RCV000461981	SCV000552444	uncertain significance	Familial adenomatous polyposis 1	2018-12-28	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.
Counsyl	RCV000461981	SCV000784763	uncertain significance	Familial adenomatous polyposis 1	2017-11-13	criteria provided, single submitter	clinical testing
Color	RCV000214073	SCV000906434	likely benign	Hereditary cancer-predisposing syndrome	2016-03-21	criteria provided, single submitter	clinical testing

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