ClinVar Miner

Submissions for variant NM_000038.6(APC):c.8146G>C (p.Val2716Leu) (rs587778044)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166038 SCV000216799 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-18 criteria provided, single submitter clinical testing Insufficient or conflicting evidence;In silico models in agreement (benign)
Invitae RCV000464425 SCV000552765 uncertain significance Familial adenomatous polyposis 1 2019-10-17 criteria provided, single submitter clinical testing This sequence change replaces valine with leucine at codon 2716 of the APC protein (p.Val2716Leu). The valine residue is weakly conserved and there is a small physicochemical difference between valine and leucine. 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: 133535). 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.
GeneDx RCV000767040 SCV000572353 uncertain significance not provided 2018-06-04 criteria provided, single submitter clinical testing This variant is denoted APC c.8146G>C at the cDNA level, p.Val2716Leu (V2716L) at the protein level, and results in the change of a Valine to a Leucine (GTG>CTG). This variant was identified in healthy East Asian individuals undergoing whole genome sequencing (Bodian 2014). Of note, the participants in this study were younger than 50 years old thus the unaffected status of these individuals may not be significant. APC Val2716Leu was not observed in large population cohorts (Lek 2016). This variant is located in the EB1 binding domain (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 Val2716Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000166038 SCV000906428 uncertain significance Hereditary cancer-predisposing syndrome 2019-12-16 criteria provided, single submitter clinical testing
ITMI RCV000120045 SCV000084179 not provided not specified 2013-09-19 no assertion provided reference population

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