ClinVar Miner

Submissions for variant NM_000038.6(APC):c.2659A>G (p.Ile887Val) (rs730881241)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159542 SCV000209505 uncertain significance not provided 2014-10-15 criteria provided, single submitter clinical testing This variant is denoted APC c.2659A>G at the cDNA level, p.Ile887Val (I887V) at the protein level, and results in the change of an Isoleucine to a Valine (ATT>GTT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Ile887Val was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Isoleucine and Valine share similar properties, this is considered a conservative amino acid substitution. APC Ile887Val occurs at a position that is highly conserved across species and is located in Ser-rich region with specific function unknown (UniProt). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether APC Ile887Val is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000204149 SCV000261962 uncertain significance Familial adenomatous polyposis 1 2018-09-06 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 887 of the APC protein (p.Ile887Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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 RCV000204149 SCV000786361 uncertain significance Familial adenomatous polyposis 1 2018-04-17 criteria provided, single submitter clinical testing

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