ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7498C>G (p.Gln2500Glu) (rs372535376)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000525604 SCV000647716 uncertain significance Familial adenomatous polyposis 1 2017-04-27 criteria provided, single submitter clinical testing This sequence change replaces glutamine with glutamic acid at codon 2500 of the APC protein (p.Gln2500Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is present in population databases (rs372535376, ExAC 0.004%) but has not been reported in the literature in individuals with an APC-related disease. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000603962 SCV000712634 uncertain significance not specified 2016-11-25 criteria provided, single submitter clinical testing The p.Gln2500Glu variant in APC has not been previously reported in individuals with APC-associated cancer, but has been identified in 3/112058 European chromos omes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.or g; dbSNP rs372535376). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summar y, the clinical significance of the p.Gln2500Glu variant is uncertain.

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