ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7550A>G (p.Tyr2517Cys) (rs587783036)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000144574 SCV000282825 uncertain significance Familial adenomatous polyposis 1 2018-12-29 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 2517 of the APC protein (p.Tyr2517Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. 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: 156483). 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). 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 RCV000759443 SCV000566783 uncertain significance not provided 2018-07-24 criteria provided, single submitter clinical testing This variant is denoted APC c.7550A>G at the cDNA level, p.Tyr2517Cys (Y2517C) at the protein level, and results in the change of a Tyrosine to a Cysteine (TAT>TGT). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. APC Tyr2517Cys 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 Tyr2517Cys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000572226 SCV000667306 uncertain significance Hereditary cancer-predisposing syndrome 2017-01-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000572226 SCV000681875 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-16 criteria provided, single submitter clinical testing
Mendelics RCV000144574 SCV000838153 uncertain significance Familial adenomatous polyposis 1 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759443 SCV000888765 uncertain significance not provided 2018-03-28 criteria provided, single submitter clinical testing
Pathway Genomics RCV000144574 SCV000189873 uncertain significance Familial adenomatous polyposis 1 2014-07-24 no assertion criteria provided clinical testing

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