Submissions for variant NM_004360.5(CDH1):c.1416C>T (p.Thr472=)

dbSNP: rs139937234

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen CDH1 Variant Curation Expert Panel	RCV003328191	SCV001142274	likely benign	CDH1-related diffuse gastric and lobular breast cancer syndrome	2023-08-17	reviewed by expert panel	curation	The c.1416C>T variant has been observed in >10 without a diagnosis of diffuse gastric cancer, signet ring tumor or lobular breast cancer and whose family histories do not suggest HDGC (BS2; internal laboratory contributors). There are at least 3 in silico predictors in agreement that this variant does not affect splicing (BP4), and the nucleotide is not conserved (BP7). Therefore, the clinical significance of this variant is likely benign. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BS2, BP4, BP7.
Invitae	RCV000123237	SCV000166543	likely benign	Hereditary diffuse gastric adenocarcinoma	2024-01-16	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000162598	SCV000213017	likely benign	Hereditary cancer-predisposing syndrome	2014-09-29	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.
Counsyl	RCV000123237	SCV000488870	likely benign	Hereditary diffuse gastric adenocarcinoma	2016-07-11	criteria provided, single submitter	clinical testing
GeneDx	RCV000433138	SCV000512521	benign	not specified	2015-03-06	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	RCV000433138	SCV000698363	likely benign	not specified	2019-08-28	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000162598	SCV000905830	likely benign	Hereditary cancer-predisposing syndrome	2015-12-09	criteria provided, single submitter	clinical testing
Mendelics	RCV000123237	SCV001140144	likely benign	Hereditary diffuse gastric adenocarcinoma	2019-05-28	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000123237	SCV004019588	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.
PreventionGenetics, part of Exact Sciences	RCV003894970	SCV004708482	likely benign	CDH1-related disorder	2021-06-07	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).