ClinVar Miner

Submissions for variant NM_000038.6(APC):c.2090C>T (p.Ala697Val) (rs761733547)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000200684 SCV000253993 uncertain significance Familial adenomatous polyposis 1 2018-10-23 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 697 of the APC protein (p.Ala697Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs761733547, ExAC 0.01%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 216153). 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 RCV000200684 SCV000488186 uncertain significance Familial adenomatous polyposis 1 2016-01-22 criteria provided, single submitter clinical testing
GeneDx RCV000657015 SCV000566393 uncertain significance not provided 2018-10-12 criteria provided, single submitter clinical testing This variant is denoted APC c.2090C>T at the cDNA level, p.Ala697Val (A697V) at the protein level, and results in the change of an Alanine to a Valine (GCA>GTA). This variant was observed in at least one individual with kidney cancer (Yehia 2018). APC Ala697Val was not observed in large population cohorts (Lek 2016). This variant is located in the Armadillo region (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 evidence, it is unclear whether APC Ala697Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000484738 SCV000600055 uncertain significance not specified 2017-07-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV000575021 SCV000667304 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000575021 SCV000686875 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-28 criteria provided, single submitter clinical testing

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