Submissions for variant NM_004360.5(CDH1):c.1689C>T (p.Ala563=)

gnomAD frequency: 0.00003  dbSNP: rs587780786

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000123240	SCV000166546	likely benign	Hereditary diffuse gastric adenocarcinoma	2024-01-24	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000162614	SCV000213045	likely benign	Hereditary cancer-predisposing syndrome	2015-01-20	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.
Illumina Laboratory Services, Illumina	RCV000123240	SCV000398567	likely 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 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	RCV000433853	SCV000512524	benign	not specified	2015-04-27	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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001281702	SCV000600964	likely benign	not provided	2019-09-16	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000162614	SCV000684376	likely benign	Hereditary cancer-predisposing syndrome	2017-05-26	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000433853	SCV001338306	likely benign	not specified	2020-02-15	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003935175	SCV004764382	likely benign	CDH1-related condition	2019-10-07	criteria provided, single submitter	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).