ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6958C>T (p.Pro2320Ser) (rs587778036)

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
Ambry Genetics RCV000568801 SCV000667320 uncertain significance Hereditary cancer-predisposing syndrome 2017-04-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Integrated Genetics/Laboratory Corporation of America RCV000589137 SCV000694105 uncertain significance not provided 2017-01-19 criteria provided, single submitter clinical testing Variant summary: The APC c.6958C>T (p.Pro2320Ser) variant involves the alteration of a conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 1/120688 control chromosomes at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic APC variant (0.0000714). The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Color RCV000568801 SCV000905994 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-09 criteria provided, single submitter clinical testing
Invitae RCV000818914 SCV000959552 uncertain significance Familial adenomatous polyposis 1 2018-08-01 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 2320 of the APC protein (p.Pro2320Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs587778036, ExAC 0.009%) but has not been reported in the literature in individuals with a APC-related disease. ClinVar contains an entry for this variant (Variation ID: 133521). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
ITMI RCV000120029 SCV000084160 not provided not specified 2013-09-19 no assertion provided reference population

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.