ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.172G>T (p.Glu58Ter)

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 RCV002407409 SCV002716717 pathogenic Hereditary cancer-predisposing syndrome 2021-05-27 criteria provided, single submitter clinical testing The p.E58* pathogenic mutation (also known as c.172G>T), located in coding exon 3 of the CDH1 gene, results from a G to T substitution at nucleotide position 172. This changes the amino acid from a glutamic acid to a stop codon within coding exon 3. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc. RCV003336713 SCV004043354 pathogenic Hereditary diffuse gastric adenocarcinoma 2023-06-08 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Baylor Genetics RCV003464533 SCV004215714 likely pathogenic Familial cancer of breast 2023-06-15 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV002407409 SCV004360436 pathogenic Hereditary cancer-predisposing syndrome 2022-08-08 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 3 of the CDH1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual with no history of diffuse gastric cancer but was found affected with signet ring cell carcinoma (SRCC) upon endoscopy (PMID: 30935944), and in several members of one family reporting no history of diffuse gastric cancer (PMID: 27064202). Clinical laboratories have classified numerous other truncations in exon 3 of CDH1 as pathogenic in ClinVar. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of CDH1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV003336713 SCV004366595 pathogenic Hereditary diffuse gastric adenocarcinoma 2023-12-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu58*) in the CDH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CDH1 are known to be pathogenic (PMID: 15235021, 20373070). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1778959). For these reasons, this variant has been classified as Pathogenic.

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.