ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7298A>G (p.Glu2433Gly) (rs730881262)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159573 SCV000209548 uncertain significance not provided 2016-01-18 criteria provided, single submitter clinical testing This variant is denoted APC c.7298A>G at the cDNA level, p.Glu2433Gly (E2433G) at the protein level, and results in the change of a Glutamic Acid to a Glycine (GAA>GGA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Glu2433Gly was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Glutamic Acid and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. APC Glu2433Gly occurs at a position that is conserved across species and is not located in a known functional domain (Azzopardi 2008, UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether APC Glu2433Gly is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000565380 SCV000667677 uncertain significance Hereditary cancer-predisposing syndrome 2016-11-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000646522 SCV000768295 uncertain significance Familial adenomatous polyposis 1 2018-12-05 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glycine at codon 2433 of the APC protein (p.Glu2433Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. 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: 181821). 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: "Probably 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.
Color RCV000565380 SCV000904041 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-11 criteria provided, single submitter clinical testing

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