ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7391C>A (p.Ser2464Tyr) (rs766473931)

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
Invitae RCV000228043 SCV000282818 uncertain significance Familial adenomatous polyposis 1 2016-03-10 criteria provided, single submitter clinical testing This sequence change replaces serine with tyrosine at codon 2464 of the APC protein (p.Ser2464Tyr). The serine residue is highly conserved and there is a large physicochemical difference between serine and tyrosine. This variant is present in population databases (rs766473931, ExAC 0.03%) but has not been reported in the literature in individuals with a APC-related disease. 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. In summary, this variant is a rare missense change with uncertain impact on 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 RCV000484267 SCV000570472 uncertain significance not provided 2016-05-24 criteria provided, single submitter clinical testing This variant is denoted APC c.7391C>A at the cDNA level, p.Ser2464Tyr (S2464Y) at the protein level, and results in the change of a Serine to a Tyrosine (TCT>TAT). This variant has not, to our knowledge, been published in the literature as either a pathogenic germline variant or a benign polymorphism. However, it has been reported as a somatic variant in The Cancer Genome Atlas of tumors (Gnad 2015). APC Ser2464Tyr 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 Serine and Tyrosine differ in some properties, this is considered a semi-conservative amino acid substitution. APC Ser2464Tyr occurs at a position that is conserved across species and is not located in a known functional domain (Azzopardi 2008). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether APC Ser2464Tyr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000776318 SCV000911647 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-10 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.