ClinVar Miner

Submissions for variant NM_000038.6(APC):c.813G>A (p.Met271Ile) (rs1064793903)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478524 SCV000567310 uncertain significance not provided 2018-05-03 criteria provided, single submitter clinical testing This variant is denoted APC c.813G>A at the cDNA level, p.Met271Ile (M271I) at the protein level, and results in the change of a Methionine to an Isoleucine (ATG>ATA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Met271Ile was not observed in large population cohorts (Lek 2016). This variant is not located in a known functional domain. 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 Met271Ile is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000539626 SCV000647757 uncertain significance Familial adenomatous polyposis 1 2018-09-07 criteria provided, single submitter clinical testing This sequence change replaces methionine with isoleucine at codon 271 of the APC protein (p.Met271Ile). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and isoleucine. 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: 419482). 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.
Ambry Genetics RCV000573645 SCV000672496 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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