ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.2602C>A (p.Arg868Ser)

gnomAD frequency: 0.00001  dbSNP: rs864622630
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
Ambry Genetics RCV000572005 SCV000661645 uncertain significance Hereditary cancer-predisposing syndrome 2022-10-21 criteria provided, single submitter clinical testing The p.R868S variant (also known as c.2602C>A), located in coding exon 16 of the CDH1 gene, results from a C to A substitution at nucleotide position 2602. The arginine at codon 868 is replaced by serine, an amino acid with dissimilar properties. This alteration has been reported in an individual affected with colorectal cancer (DeRycke MS et al. Mol Genet Genomic Med, 2017 Sep;5:553-569). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000572005 SCV000906484 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-20 criteria provided, single submitter clinical testing This missense variant replaces arginine with serine at codon 868 of the CDH1 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/31396 chromosomes 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001037253 SCV001200657 uncertain significance Hereditary diffuse gastric adenocarcinoma 2023-03-30 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 479500). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 868 of the CDH1 protein (p.Arg868Ser). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Diagnostics Services (NGS), CSIR - Centre For Cellular And Molecular Biology RCV001799514 SCV002043756 uncertain significance Familial cancer of breast; Blepharocheilodontic syndrome 1; Hereditary diffuse gastric adenocarcinoma; Malignant tumor of prostate 2021-10-12 criteria provided, single submitter clinical testing The c.2602C>A variant is not present in publicly available population databases like 1000 Genomes, Exome Variant Server (EVS), Exome Aggregation Consortium (ExAC) and Genome Aggregation Database (gnomAD). The variant is not present in Indian Exome Database and in our in-house exome database. The variant was earlier reported to ClinVar (Accession: VCV000220695.10) several times as uncertain significance in association with hereditary cancer predisposing syndrome. CDH1 Arg868Cys occurs at a position that is conserved across species and there is a large physicochemical difference between arginine and cysteine. In-silico pathogenicity prediction programs like SIFT, Polyphen-2, MutationTaster2, CADD etc. predicted this variant to be likely disease causing as it may probably damage the protein structure and function. Varsome predicted this variant as VUS with minor pathogenic evidence but these predictions have not been confirmed by published functional studies and it's clinical significance is uncertain.
Baylor Genetics RCV004569100 SCV005060069 uncertain significance Familial cancer of breast 2024-02-29 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.