ClinVar Miner

Submissions for variant NM_000038.6(APC):c.2855C>T (p.Ala952Val) (rs776560257)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235602 SCV000293559 uncertain significance not provided 2017-11-22 criteria provided, single submitter clinical testing This variant is denoted APC c.2855C>T at the cDNA level, p.Ala952Val (A952V) at the protein level, and results in the change of an Alanine to a Valine (GCC>GTC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Ala952Val was not observed at a significant allele frequency in large population cohorts (Lek 2016). Since Alanine and Valine share similar properties, this is considered a conservative amino acid substitution. APC Ala952Val is not located in a known functional domain. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure or function. Based on currently available evidence, it is unclear whether APC Ala952Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000537016 SCV000647276 uncertain significance Familial adenomatous polyposis 1 2018-12-26 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 952 of the APC protein (p.Ala952Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with familial adenomatous polyposis (FAP) in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 246136). 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. 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 RCV000566278 SCV000667302 uncertain significance Hereditary cancer-predisposing syndrome 2017-03-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000566278 SCV000906625 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-21 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000235602 SCV001154460 uncertain significance not provided 2018-07-01 criteria provided, single submitter clinical testing

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