ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.2104G>T (p.Glu702Ter)

dbSNP: rs149127230
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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 RCV003328397 SCV001142221 pathogenic CDH1-related diffuse gastric and lobular breast cancer syndrome 2023-08-04 reviewed by expert panel curation The c.2104G>T (p.Glu702Ter) variant is predicted to result in a premature stop codon that leads to nonsense mediate decay (PVS1 and PM5_supporting). The variant is absent in the gnomAD cohort (PM2_supporting; http://gnomad.broadinstitute.org). Therefore, this variant meets criteria to be classified as pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (CDH1 VCEP specifications version 3.1): PVS1, PM2_supporting, PM5_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV000530851 SCV000637773 pathogenic Hereditary diffuse gastric adenocarcinoma 2017-10-10 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.Glu702*) in the CDH1 gene. It is expected to result in an absent or disrupted protein product.
Ambry Genetics RCV002420415 SCV002724580 pathogenic Hereditary cancer-predisposing syndrome 2021-03-17 criteria provided, single submitter clinical testing The p.E702* pathogenic mutation (also known as c.2104G>T), located in coding exon 13 of the CDH1 gene, results from a G to T substitution at nucleotide position 2104. This changes the amino acid from a glutamic acid to a stop codon within coding exon 13. 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.

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