ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7793C>A (p.Thr2598Asn) (rs747339588)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000232733 SCV000282831 uncertain significance Familial adenomatous polyposis 1 2018-10-30 criteria provided, single submitter clinical testing This sequence change replaces threonine with asparagine at codon 2598 of the APC protein (p.Thr2598Asn). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and asparagine. This variant is present in population databases (rs747339588, ExAC 0.002%) but has not been reported in the literature in individuals with a APC-related disease. ClinVar contains an entry for this variant (Variation ID: 236649). 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 tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000766657 SCV000293216 uncertain significance not provided 2015-10-05 criteria provided, single submitter clinical testing This variant is denoted APC c.7793C>A at the cDNA level, p.Thr2598Asn (T2598N) at the protein level, and results in the change of a Threonine to an Asparagine (ACC>AAC). This variant has not, to our knowledge, been published in the literature as being pathogenic or benign. APC Thr2598Asn was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Threonine and Asparagine share similar properties, this is considered a conservative amino acid substitution. APC Thr2598Asn occurs at a position that is not conserved and is located in the EB1 domain (Azzopardi 2008). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether APC Thr2598Asn is pathogenic or benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000235712 SCV000600161 uncertain significance not specified 2017-05-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV000563888 SCV000667299 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000563888 SCV000681887 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-18 criteria provided, single submitter clinical testing

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.