ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6952A>G (p.Ser2318Gly) (rs747056590)

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
GeneDx RCV000588074 SCV000566117 uncertain significance not provided 2017-06-08 criteria provided, single submitter clinical testing This variant is denoted APC c.6952A>G at the cDNA level, p.Ser2318Gly (S2318G) at the protein level, and results in the change of a Serine to a Glycine (AGT>GGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Ser2318Gly was not observed at a significant allele frequency in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Serine and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. APC Ser2318Gly occurs at a position where amino acids with properties similar to Serine are tolerated across species and is located in the Basic domain (Azzopardi 2008). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether APC Ser2318Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000563979 SCV000667442 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Integrated Genetics/Laboratory Corporation of America RCV000588074 SCV000694104 uncertain significance not provided 2017-03-13 criteria provided, single submitter clinical testing Variant summary: The APC c.6952A>G (p.Ser2318Gly) variant located in the adenomatous polyposis coli protein basic domain (via InterPro) involves the alteration of a conserved nucleotide that 3/4 in silico tools (SNPs&GO not captured due to low reliability index) predict a damaging outcome, although these predictions have yet to be functionally assessed. The variant of interest has been observed in the large, broad control population, ExAC, with an allele frequency of 1/120752, which does not exceed the estimated maximal expected allele frequency for a pathogenic APC variant of 1/14005. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. Therefore, until additional information becomes available (ie, clinical and functional studies), the variant of interest has been classified as a "Variant of Uncertain Significance."
Invitae RCV000686468 SCV000813987 uncertain significance Familial adenomatous polyposis 1 2018-11-19 criteria provided, single submitter clinical testing This sequence change replaces serine with glycine at codon 2318 of the APC protein (p.Ser2318Gly). The serine residue is highly conserved and there is a small physicochemical difference between serine and glycine. This variant is present in population databases (rs747056590, ExAC 0.009%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 418792). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; 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 RCV000563979 SCV000909623 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-24 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.