ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.2505_2506dup (p.Glu836fs)

dbSNP: rs1555518236
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen CDH1 Variant Curation Expert Panel RCV003328411 SCV001437616 uncertain significance CDH1-related diffuse gastric and lobular breast cancer syndrome 2023-08-04 reviewed by expert panel curation The c.2505_2506dupTG (p.Glu836ValfsTer11) variant results in a premature stop codon that leads to a truncated protein. It is located within the nonsense mediated decay resistant zone, and downstream of codon 836 where the most 3' pathogenic variant in CDH1 terminates (PVS1_Moderate, PMID: 29798843). This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). In summary, the clinical significance of this variant is uncertain based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel: PVS1_Moderate, PM2_Supporting.
Ambry Genetics RCV000565359 SCV000665390 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-03 criteria provided, single submitter clinical testing The c.2505_2506dupTG variant, located in coding exon 16 of the CDH1 gene, results from a duplication of TG at nucleotide position 2505, causing a translational frameshift with a predicted alternate stop codon (p.E836Vfs*11). Frameshifts are typically deleterious in nature, however, this frameshift occurs at the 3' terminus of CDH1, is not expected to trigger nonsense-mediated mRNA decay, and impacts only the last 47 amino acids of the protein. The exact functional impact of these altered amino acids is unknown at this time. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Myriad Genetics, Inc. RCV003451239 SCV004189612 likely pathogenic Hereditary diffuse gastric adenocarcinoma 2023-11-20 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

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