Submissions for variant NM_004360.5(CDH1):c.2280C>T (p.Gly760=)

gnomAD frequency: 0.00004  dbSNP: rs768547540

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000162719	SCV000213181	likely benign	Hereditary cancer-predisposing syndrome	2014-09-26	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	RCV000197865	SCV000253419	likely benign	Hereditary diffuse gastric adenocarcinoma	2024-01-29	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000162719	SCV000684415	likely benign	Hereditary cancer-predisposing syndrome	2015-04-23	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000197865	SCV001274531	likely benign	Hereditary diffuse gastric adenocarcinoma	2018-01-13	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx	RCV001618319	SCV001845664	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000162719	SCV002529120	likely benign	Hereditary cancer-predisposing syndrome	2020-10-01	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002465541	SCV002760864	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149991	SCV003838419	likely benign	Breast and/or ovarian cancer	2022-05-17	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	RCV000197865	SCV003926911	uncertain significance	Hereditary diffuse gastric adenocarcinoma	2022-08-01	criteria provided, single submitter	clinical testing	Not applicable criteria (PMID: 30311375)
Myriad Genetics, Inc.	RCV000197865	SCV005405275	benign	Hereditary diffuse gastric adenocarcinoma	2024-09-23	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.
PreventionGenetics, part of Exact Sciences	RCV003945258	SCV004763556	likely benign	CDH1-related disorder	2020-07-09	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).