ClinVar Miner

Submissions for variant NM_000038.5(APC):c.4333A>G (p.Thr1445Ala) (rs587780597)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000567758 SCV000667288 uncertain significance Hereditary cancer-predisposing syndrome 2018-02-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Color RCV000567758 SCV000903135 likely benign Hereditary cancer-predisposing syndrome 2017-02-28 criteria provided, single submitter clinical testing
Counsyl RCV000122780 SCV000487868 uncertain significance Familial adenomatous polyposis 1 2015-12-04 criteria provided, single submitter clinical testing
GeneDx RCV000428958 SCV000520875 likely benign not specified 2018-01-26 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000122780 SCV000166037 uncertain significance Familial adenomatous polyposis 1 2018-05-01 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 1445 of the APC protein (p.Thr1445Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs587780597, ExAC 0.003%). This variant has been reported in an individual affected with colorectal adenomas (PMID: 18199528). ClinVar contains an entry for this variant (Variation ID: 135702). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional 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.
Mendelics RCV000122780 SCV000838116 uncertain significance Familial adenomatous polyposis 1 2018-07-02 criteria provided, single submitter clinical testing

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