Submissions for variant NM_004360.5(CDH1):c.1605del (p.Asn536fs)

dbSNP: rs1596960393

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000797442	SCV000936999	pathogenic	Hereditary diffuse gastric adenocarcinoma	2021-02-15	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 disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Asn536Ilefs*21) in the CDH1 gene. It is expected to result in an absent or disrupted protein product.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001283956	SCV001469485	pathogenic	not provided	2020-05-29	criteria provided, single submitter	clinical testing	The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and not found in general population data.
Color Diagnostics, LLC DBA Color Health	RCV001525052	SCV001735053	pathogenic	Hereditary cancer-predisposing syndrome	2021-08-30	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 11 of the CDH1 gene, creating a frameshift and 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.
Ambry Genetics	RCV001525052	SCV002703594	pathogenic	Hereditary cancer-predisposing syndrome	2019-03-27	criteria provided, single submitter	clinical testing	The c.1605delT pathogenic mutation, located in coding exon 11 of the CDH1 gene, results from a deletion of one nucleotide at nucleotide position 1605, causing a translational frameshift with a predicted alternate stop codon (p.N536Ifs*21). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc.	RCV000797442	SCV004042969	pathogenic	Hereditary diffuse gastric adenocarcinoma	2023-06-14	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.