Submissions for variant NM_004360.5(CDH1):c.888C>A (p.Tyr296Ter)

dbSNP: rs895188181

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001232101	SCV001404647	pathogenic	Hereditary diffuse gastric adenocarcinoma	2019-10-29	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in CDH1 are known to be pathogenic (PMID: 15235021, 20373070). This variant has not been reported in the literature in individuals with CDH1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr296*) in the CDH1 gene. It is expected to result in an absent or disrupted protein product.
Color Diagnostics, LLC DBA Color Health	RCV001524548	SCV001734439	pathogenic	Hereditary cancer-predisposing syndrome	2020-05-11	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 7 of the CDH1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of CDH1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.