ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.650G>T (p.Arg217Ile)

dbSNP: rs1486909310
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000533182 SCV000633204 uncertain significance Familial cancer of breast 2017-05-23 criteria provided, single submitter clinical testing In summary, this variant has uncertain impact on CHEK2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with a CHEK2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with isoleucine at codon 217 of the CHEK2 protein (p.Arg217Ile). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and isoleucine.
Color Diagnostics, LLC DBA Color Health RCV003584653 SCV004361390 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-16 criteria provided, single submitter clinical testing This missense variant replaces arginine with isoleucine at codon 217 of the CHEK2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with CHEK2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of 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.