ClinVar Miner

Submissions for variant NM_000038.6(APC):c.8321G>C (p.Ser2774Thr) (rs863224553)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000196149 SCV000254048 uncertain significance Familial adenomatous polyposis 1 2018-08-16 criteria provided, single submitter clinical testing This sequence change replaces serine with threonine at codon 2774 of the APC protein (p.Ser2774Thr). The serine residue is highly conserved and there is a small physicochemical difference between serine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 216186). 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 tolerated, but 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 RCV000196149 SCV000488262 uncertain significance Familial adenomatous polyposis 1 2016-02-12 criteria provided, single submitter clinical testing
Color RCV000582316 SCV000687173 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-26 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589226 SCV000694142 uncertain significance not provided 2016-06-06 criteria provided, single submitter clinical testing Variant summary: The APC c.8321G>C (p.Ser2774Thr) variant involves the alteration of a conserved nucleotide. 3/5 in silico tools predict a benign outcome. This variant is absent in 120804 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies, but has been reported by a reputable clinical lab as a VUS. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.

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