Submissions for variant NM_004360.5(CDH1):c.1161C>T (p.Asn387=)

gnomAD frequency: 0.00003  dbSNP: rs111266450

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163636	SCV000214204	likely benign	Hereditary cancer-predisposing syndrome	2015-04-02	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	RCV000228646	SCV000288422	benign	Hereditary diffuse gastric adenocarcinoma	2025-01-30	criteria provided, single submitter	clinical testing
Counsyl	RCV000228646	SCV000488617	likely benign	Hereditary diffuse gastric adenocarcinoma	2016-05-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000430737	SCV000512518	benign	not specified	2015-06-09	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000430737	SCV000919110	benign	not specified	2018-08-27	criteria provided, single submitter	clinical testing	Variant summary: CDH1 c.1161C>T results in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 6.5e-05 in 277224 control chromosomes. The observed variant frequency is approximately 2.3-fold above the estimated maximal expected allele frequency for a pathogenic variant in CDH1 causing Hereditary Diffuse Gastric Cancer phenotype (2.8e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1161C>T in individuals affected with Hereditary Diffuse Gastric Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Color Diagnostics, LLC DBA Color Health	RCV000163636	SCV001736020	likely benign	Hereditary cancer-predisposing syndrome	2016-04-26	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163636	SCV002531143	benign	Hereditary cancer-predisposing syndrome	2022-02-24	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000430737	SCV002551766	likely benign	not specified	2025-03-04	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	RCV000228646	SCV003926750	uncertain significance	Hereditary diffuse gastric adenocarcinoma	2022-08-01	criteria provided, single submitter	clinical testing	Not applicable criteria (PMID: 30311375)
Myriad Genetics, Inc.	RCV000228646	SCV004019991	benign	Hereditary diffuse gastric adenocarcinoma	2023-03-06	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV003477597	SCV004220777	benign	not provided	2023-04-04	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003945272	SCV004762648	likely benign	CDH1-related disorder	2019-10-31	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).