CDH1 Variant Curation Expert Panel


Pathogenic germline variants in CDH1 have been associated with hereditary diffuse gastric cancer
(HDGC, MIM# 137215), an autosomal dominant cancer predisposition syndrome. Heterozygous CDH1
carriers of pathogenic variants have a significantly increased risk of developing diffuse gastric cancer
(DGC). In addition to gastric cancer, female heterozygous carriers are at risk of developing lobular
carcinoma of the breast. Identification of CDH1 carriers is important, because the characteristic
microscopic foci of signet ring cell adenocarcinoma in HDGC usually involves the submucosa and is
often not readily detectable by routine upper endoscopy screening (Fitzgerald et al., 2010). Due to the
aggressive nature of DGC, the clinical management recommendation for risk reduction is prophylactic
gastrectomy. Given the quality of life issues as a consequence of this preventative and irreversible
surgery, it is imperative that patients and their providers be given high quality information while trying to
limit uncertainty. This Expert Panel will provide assessment regarding the pathogenicity of variants in
CDH1 with respect to a HDGC phenotype.

Expert Status - Approved Expert Panel

Step 1
Step 2
Step 3
Step 4
Define Group
Complete
Develop Classification Rules
Complete
Pilot Rules
Complete
Expert Panel Approval
Complete

Leadership

Rachid Karam, MD, PhD

Intan Schrader, MBBS, FRCPC, PhD, DABMG


Coordinators

Please contact a coordinator if you have questions.

Xi Luo, PhD
xi.luo@bcm.edu

Kristy Lee, MS, CGC


Membership

Membership in this committee spans many fields, including genetics, medical, academia, and industry. [View Members]
For more information, please contact:

Xi Luo, PhD
xi.luo@bcm.edu

Kristy Lee, MS, CGC


What is VARIANT CURATION?

A systematic process of evaluating evidence to classify a genomic variant on a spectrum from pathogenic to benign with respect to a particular disease and inheritance pattern.