Submissions for variant NM_004360.5(CDH1):c.1020G>A (p.Thr340=)

gnomAD frequency: 0.00008  dbSNP: rs61747632

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000212360	SCV000210881	benign	not specified	2014-08-01	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.
Ambry Genetics	RCV000160372	SCV000213321	likely benign	Hereditary cancer-predisposing syndrome	2014-09-09	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
Invitae	RCV000198410	SCV000252787	benign	Hereditary diffuse gastric adenocarcinoma	2024-01-30	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000198410	SCV000398559	benign	Hereditary diffuse gastric adenocarcinoma	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Color Diagnostics, LLC DBA Color Health	RCV000160372	SCV000684325	likely benign	Hereditary cancer-predisposing syndrome	2015-04-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588315	SCV000698352	benign	not provided	2016-08-08	criteria provided, single submitter	clinical testing	Variant summary: The CDH1 c.1020G>A (p.Thr340Thr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. Mutation taster predicts a damaging outcome for this variant while splice prediction tools indicate the variant not to have an impact on normal splicing. This variant was found in 22/121410 control chromosomes (1 homozygote), predominantly observed in the East Asian subpopulation at a frequency of 0.00104 (9/8654). This frequency is about 37 times the estimated maximal expected allele frequency of a pathogenic CDH1 variant (0.0000283), suggesting this is likely a benign polymorphism found primarily in the populations of East Asian origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign.
Counsyl	RCV000198410	SCV000786161	likely benign	Hereditary diffuse gastric adenocarcinoma	2018-03-12	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000588315	SCV000889234	benign	not provided	2022-08-04	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798549	SCV002043247	likely benign	Breast and/or ovarian cancer	2022-04-29	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000212360	SCV002067078	likely benign	not specified	2021-01-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000160372	SCV002531136	benign	Hereditary cancer-predisposing syndrome	2021-10-11	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000212360	SCV002760856	likely benign	not specified	2023-08-15	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	RCV000198410	SCV003926723	likely benign	Hereditary diffuse gastric adenocarcinoma	2022-08-01	criteria provided, single submitter	clinical testing	BS1; BP2 (PMID: 30311375)
Myriad Genetics, Inc.	RCV000198410	SCV004019985	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.
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000588315	SCV001957952	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000588315	SCV001966084	likely benign	not provided		no assertion criteria provided	clinical testing