ClinVar Miner

Submissions for variant NM_000038.6(APC):c.262C>T (p.Arg88Trp) (rs746592911)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766533 SCV000569765 uncertain significance not provided 2018-07-27 criteria provided, single submitter clinical testing This variant is denoted APC c.262C>T at the cDNA level, p.Arg88Trp (R88W) at the protein level, and results in the change of an Arginine to a Tryptophan (CGG>TGG). This variant was observed in two controls in a case-control study of schizophrenia, with no specific information about cancer history (Purcell 2014). APC Arg88Trp was not observed at a significant allele frequency in large population cohorts (Lek 2016). APC Arg88Trp is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether APC Arg88Trp is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000484135 SCV000591021 uncertain significance not specified 2015-10-29 criteria provided, single submitter clinical testing
Ambry Genetics RCV000574492 SCV000667444 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Color RCV000574492 SCV000681542 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-15 criteria provided, single submitter clinical testing
Invitae RCV000646444 SCV000768216 uncertain significance Familial adenomatous polyposis 1 2018-10-08 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 88 of the APC protein (p.Arg88Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs746592911, 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: 420793). 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 disruptive, 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.
Mendelics RCV000646444 SCV000838058 uncertain significance Familial adenomatous polyposis 1 2018-07-02 criteria provided, single submitter clinical testing

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