ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.1136C>T (p.Thr379Met)

gnomAD frequency: 0.00001  dbSNP: rs587782856
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 11
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen CDH1 Variant Curation Expert Panel RCV003328235 SCV004035106 likely benign CDH1-related diffuse gastric and lobular breast cancer syndrome 2023-08-03 reviewed by expert panel curation The c.1136C>T (p.Thr379Met) variant results in a conservative missense change in the Cadherin 3 domain of CDH1. This variant was observed in 2 of 152,226 alleles in the gnomAD population database. However, this variants has also been observed in more than 10 individuals without GC, DGC, gastric SRC tumours or LBC and whose families do not suggest HDGC (BS2). In summary, this variant meets criteria to be classified as Likely Benign based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel: BS2. (CDH1 VCEP specifications version 3.1; 05/22/2023)
Ambry Genetics RCV000132465 SCV000187559 likely benign Hereditary cancer-predisposing syndrome 2021-02-16 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp RCV000227986 SCV000288419 benign Hereditary diffuse gastric adenocarcinoma 2025-01-30 criteria provided, single submitter clinical testing
Counsyl RCV000227986 SCV000488775 uncertain significance Hereditary diffuse gastric adenocarcinoma 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000480330 SCV000567843 uncertain significance not provided 2022-12-02 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 30836094, 30766968, 31871109, 15235021, 22850631)
Color Diagnostics, LLC DBA Color Health RCV000132465 SCV000684329 likely benign Hereditary cancer-predisposing syndrome 2024-01-05 criteria provided, single submitter clinical testing
Mendelics RCV000227986 SCV000839086 uncertain significance Hereditary diffuse gastric adenocarcinoma 2018-07-02 criteria provided, single submitter clinical testing
European Reference Network on Genetic Tumour Risk Syndromes (ERN-GENTURIS), i3s - Instituto de Investigação e Inovação em Saúde, University of Porto RCV000227986 SCV003926732 uncertain significance Hereditary diffuse gastric adenocarcinoma 2022-08-01 criteria provided, single submitter clinical testing PM2 (PMID: 30311375)
Myriad Genetics, Inc. RCV000227986 SCV004020008 uncertain significance Hereditary diffuse gastric adenocarcinoma 2023-03-06 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000480330 SCV004563165 uncertain significance not provided 2023-09-14 criteria provided, single submitter clinical testing The CDH1 c.1136C>T; p.Thr379Met variant (rs587782856) is reported in the literature in individuals affected with cancer (Garcia-Pelaez 2023, Guindalini 2022). This variant is reported in ClinVar (Variation ID: 142968), and is found in the general population with an overall allele frequency of 0.002% (4/251,460 alleles) in the Genome Aggregation Database. Computational analyses predict that this variant is neutral (REVEL: 0.03). Due to limited information, the clinical significance of this variant is uncertain at this time. References: Garcia-Pelaez J et al. Genotype-first approach to identify associations between CDH1 germline variants and cancer phenotypes: a multicentre study by the European Reference Network on Genetic Tumour Risk Syndromes. Lancet Oncol. 2023 Jan;24(1):91-106. PMID: 36436516. Guindalini RSC et al. Detection of germline variants in Brazilian breast cancer patients using multigene panel testing. Sci Rep. 2022 Mar 9;12(1):4190. PMID: 35264596.
Fulgent Genetics, Fulgent Genetics RCV005016460 SCV005644339 uncertain significance Familial cancer of breast; Blepharocheilodontic syndrome 1; Endometrial carcinoma; Hereditary diffuse gastric adenocarcinoma; Ovarian cancer 2023-12-28 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.