Submissions for variant NM_004360.5(CDH1):c.2416G>T (p.Glu806Ter)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV003182774	SCV003867732	likely pathogenic	Hereditary cancer-predisposing syndrome	2022-12-01	criteria provided, single submitter	clinical testing	The p.E806* variant (also known as c.2416G>T), located in coding exon 15 of the CDH1 gene, results from a G to T substitution at nucleotide position 2416. This changes the amino acid from a glutamic acid to a stop codon within coding exon 15. This alteration occurs at the 3' terminus of theCDH1 gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 77 amino acids of the protein. However, premature stop codons are typically deleterious in nature, the impacted region is critical for protein function and a significant portion of the protein is affected (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Myriad Genetics, Inc.	RCV003336831	SCV004043436	pathogenic	Hereditary diffuse gastric adenocarcinoma	2023-06-15	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV003336831	SCV005417019	likely pathogenic	Hereditary diffuse gastric adenocarcinoma		criteria provided, single submitter	clinical testing	PM2_Supporting+PVS1_Strong+PS4_Supporting