ClinVar Miner

Submissions for variant NM_000038.6(APC):c.918T>G (p.Ser306Arg) (rs730881231)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159528 SCV000209487 uncertain significance not provided 2014-08-29 criteria provided, single submitter clinical testing This variant is denoted APC c.918T>G at the cDNA level, p.Ser306Arg (S306R) at the protein level, and results in the change of a Serine to an Arginine (AGT>AGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Ser306Arg 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 Serine and Arginine differ in some properties, this is considered a semi-conservative amino acid substitution. APC Ser306Arg occurs at a position that is conserved across species and is not located in a known functional domain. In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether APC Ser306Arg is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000217691 SCV000273639 uncertain significance Hereditary cancer-predisposing syndrome 2018-01-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000466236 SCV000552619 uncertain significance Familial adenomatous polyposis 1 2018-11-15 criteria provided, single submitter clinical testing This sequence change replaces serine with arginine at codon 306 of the APC protein (p.Ser306Arg). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and arginine. This variant is present in population databases (rs730881231, ExAC 0.005%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 181783). 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 and their clinical significance is uncertain. 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 RCV000217691 SCV000681937 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-06 criteria provided, single submitter clinical testing
Counsyl RCV000466236 SCV000785980 uncertain significance Familial adenomatous polyposis 1 2018-01-25 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000779736 SCV000916504 uncertain significance not specified 2019-09-06 criteria provided, single submitter clinical testing Variant summary: APC c.918T>G (p.Ser306Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251136 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.918T>G in individuals affected with Familial Adenomatous Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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.