ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.1569T>A (p.Tyr523Ter)

dbSNP: rs876659716
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen CDH1 Variant Curation Expert Panel RCV003328407 SCV001365416 pathogenic CDH1-related diffuse gastric and lobular breast cancer syndrome 2023-08-04 reviewed by expert panel curation The c.1569T>A p.(Tyr523Ter) 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.
Ambry Genetics RCV000561178 SCV000661672 pathogenic Hereditary cancer-predisposing syndrome 2017-02-10 criteria provided, single submitter clinical testing The p.Y523* pathogenic mutation (also known as c.1569T>A), located in coding exon 11 of the CDH1 gene, results from a T to A substitution at nucleotide position 1569. This changes the amino acid from a tyrosine to a stop codon within coding exon 11. 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000702111 SCV000830946 pathogenic Hereditary diffuse gastric adenocarcinoma 2022-10-23 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 479518). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr523*) in the CDH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CDH1 are known to be pathogenic (PMID: 15235021, 20373070).
Myriad Genetics, Inc. RCV000702111 SCV004189627 pathogenic Hereditary diffuse gastric adenocarcinoma 2023-11-07 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.

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