ClinVar Miner

Submissions for variant NM_000038.6(APC):c.2677G>A (p.Glu893Lys) (rs199740875)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164189 SCV000214810 uncertain significance Hereditary cancer-predisposing syndrome 2018-02-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Counsyl RCV000409913 SCV000489375 uncertain significance Familial adenomatous polyposis 1 2016-10-03 criteria provided, single submitter clinical testing
Invitae RCV000409913 SCV000552459 uncertain significance Familial adenomatous polyposis 1 2018-04-11 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 893 of the APC protein (p.Glu893Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs199740875, ExAC 0.009%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 41501). 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: "Possibly Damaging"; 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.
Color RCV000164189 SCV000681546 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-07 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000034383 SCV000694017 uncertain significance not provided 2016-05-20 criteria provided, single submitter clinical testing Variant summary: The APC c.2677G>A (p.Glu893Lys) variant involves the alteration of a conserved nucleotide. 4/5 in silico tools predict a damaging outcome. This variant was found in 7/122460 control chromosomes, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.0000899 (6/66710). This frequency is about 1.25 times the estimated maximal expected allele frequency of a pathogenic APC variant (0.0000714), suggesting this is may be a benign polymorphism found primarily in the populations of European (Non-Finnish) origin. Multiple clinical diagnostic laboratories/reputable databases classified this variant as a VUS. 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. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a VUS - Possibly Benign, until additional information becomes available.
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034383 SCV000043117 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.

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