Submissions for variant NM_004360.5(CDH1):c.1272C>T (p.Val424=)

gnomAD frequency: 0.00143  dbSNP: rs61756284

Total submissions: 22

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000212363	SCV000167593	benign	not specified	2014-01-13	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	RCV000124179	SCV000212843	benign	Hereditary cancer-predisposing syndrome	2019-10-07	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Invitae	RCV001083285	SCV000252790	benign	Hereditary diffuse gastric adenocarcinoma	2024-02-01	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000488346	SCV000575056	likely benign	not provided	2024-04-01	criteria provided, single submitter	clinical testing	CDH1: BP4, BP7, BS1
Color Diagnostics, LLC DBA Color Health	RCV000124179	SCV000684348	likely benign	Hereditary cancer-predisposing syndrome	2015-10-19	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000488346	SCV000698357	benign	not provided	2016-06-20	criteria provided, single submitter	clinical testing	Variant summary: The CDH1 c.1272C>T (p.Val424Val) variant causes a synonymous change involving a non-conserved nucleotide with 5/5 splice prediction tools predicting no significant effect on splicing, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 94/121412 (1/1292), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic CDH1 variant of 1/35336 (0.0000283), suggesting this variant is likely a benign polymorphism. Mulitple reputable clinical laboratories cite the variant as "likely benign/benign." Therefore, taking all available lines of evidence into consideration and based on the high allele frequency in the general population, the variant of interest has been classified as Benign.
PreventionGenetics, part of Exact Sciences	RCV003891656	SCV000806634	benign	CDH1-related disorder	2020-08-08	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000488346	SCV000883549	benign	not provided	2022-11-28	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000212363	SCV000889245	benign	not specified	2021-05-17	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000488346	SCV002009864	likely benign	not provided	2021-11-03	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798417	SCV002043249	likely benign	Breast and/or ovarian cancer	2023-03-09	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000212363	SCV002064828	likely benign	not specified	2022-01-04	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000124179	SCV002531154	benign	Hereditary cancer-predisposing syndrome	2021-01-09	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000212363	SCV002551770	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	RCV001083285	SCV003926764	likely benign	Hereditary diffuse gastric adenocarcinoma	2022-08-01	criteria provided, single submitter	clinical testing	BS1; BS2_Supporting (PMID: 30311375)
Mayo Clinic Laboratories, Mayo Clinic	RCV000212363	SCV000691819	likely benign	not specified		no assertion criteria provided	clinical testing
True Health Diagnostics	RCV000124179	SCV000787974	likely benign	Hereditary cancer-predisposing syndrome	2017-10-11	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000488346	SCV001742115	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000212363	SCV001809278	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000212363	SCV001923364	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000212363	SCV001953596	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000212363	SCV001968963	benign	not specified		no assertion criteria provided	clinical testing