ClinVar Miner

Submissions for variant NM_000038.6(APC):c.8518G>A (p.Val2840Met)

dbSNP: rs878853480
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000772143 SCV000905247 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-16 criteria provided, single submitter clinical testing This missense variant replaces valine with methionine at codon 2840 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with APC-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae RCV000226457 SCV002180987 uncertain significance Familial adenomatous polyposis 1 2022-10-13 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 2840 of the APC protein (p.Val2840Met). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 236660). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APC protein function. 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.
Ambry Genetics RCV000772143 SCV004005202 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-10 criteria provided, single submitter clinical testing The p.V2840M variant (also known as c.8518G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 8518. The valine at codon 2840 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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