ClinVar Miner

Submissions for variant NM_000038.6(APC):c.2782G>A (p.Ala928Thr)

dbSNP: rs730881222
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159509 SCV000209464 uncertain significance not provided 2018-07-02 criteria provided, single submitter clinical testing This variant is denoted APC c.2782G>A at the cDNA level, p.Ala928Thr (A928T) at the protein level, and results in the change of an Alanine to a Threonine (GCC>ACC). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. APC Ala928Thr 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 Ala928Thr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV003534395 SCV000955001 uncertain significance Familial adenomatous polyposis 1 2023-07-29 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 928 of the APC protein (p.Ala928Thr). This variant is present in population databases (rs730881222, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 181768). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APC protein function. 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.
Ambry Genetics RCV002433712 SCV002748253 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-03 criteria provided, single submitter clinical testing The p.A928T variant (also known as c.2782G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 2782. The alanine at codon 928 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.