ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.1633C>T (p.Arg545Trp) (rs863224727)

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 RCV000639204 SCV000760773 uncertain significance Hereditary diffuse gastric cancer 2017-09-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 545 of the CDH1 protein (p.Arg545Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CDH1-related disease. 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, 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 RCV001175686 SCV001339380 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-28 criteria provided, single submitter clinical testing
MVZ Praenatalmedizin und Genetik Nuernberg RCV000515474 SCV000611131 uncertain significance Familial cancer of breast 2017-11-01 no assertion criteria provided clinical testing This rare/private variant (gnomAD: 1/246266 alleles) was not found in databases and literature, only 1 COSMIC-entry. Multiple in silico analyses are contradictory. Therefore we rate this variant as Variant of unknown significance (VUS)

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.