ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.1296C>G (p.Asn432Lys) (rs187862045)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166605 SCV000217409 uncertain significance Hereditary cancer-predisposing syndrome 2017-11-13 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV000460665 SCV000545471 uncertain significance Hereditary diffuse gastric cancer 2018-08-28 criteria provided, single submitter clinical testing This sequence change replaces asparagine with lysine at codon 432 of the CDH1 protein (p.Asn432Lys). The asparagine residue is highly conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is present in population databases (rs187862045, ExAC 0.03%). This variant has been reported in individuals affected with gastric cancer (PMID: 23435907) and breast cancer (PMID: 25927356). ClinVar contains an entry for this variant (Variation ID: 186937). An experimental study has shown that an abnormal mRNA transcript, lacking exon 9, was detected in a gastric tumor sample from an individual carrying this variant (PMID: 23425907). However, this transcript was not detected in normal tissues from this individual, suggesting that it could be the result of a somatic change. 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: "Tolerated"; 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 RCV000166605 SCV000903557 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-22 criteria provided, single submitter clinical testing
3DMed Clinical Laboratory Inc RCV000677870 SCV000804031 likely pathogenic Neoplasm of stomach 2017-12-08 no assertion criteria provided 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.