ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7531C>T (p.Leu2511Phe) (rs72541815)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166364 SCV000217153 uncertain significance Hereditary cancer-predisposing syndrome 2016-07-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000473143 SCV000552783 uncertain significance Familial adenomatous polyposis 1 2018-11-18 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 2511 of the APC protein (p.Leu2511Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is present in population databases (rs72541815, ExAC 0.009%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 186722). 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: "Possibly Damaging"; 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.
GeneDx RCV000482783 SCV000566845 uncertain significance not provided 2018-11-12 criteria provided, single submitter clinical testing This variant is denoted APC c.7531C>T at the cDNA level, p.Leu2511Phe (L2511F) at the protein level, and results in the change of a Leucine to a Phenylalanine (CTC>TTC). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. APC Leu2511Phe was not observed at a significant allele frequency 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 Leu2511Phe is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000166364 SCV000681873 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-03 criteria provided, single submitter clinical testing
Counsyl RCV000473143 SCV000785039 uncertain significance Familial adenomatous polyposis 1 2017-03-20 criteria provided, single submitter clinical testing

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