ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.11G>A (p.Trp4Ter)

dbSNP: rs1962423346
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen CDH1 Variant Curation Expert Panel RCV003328476 SCV001943352 pathogenic CDH1-related diffuse gastric and lobular breast cancer syndrome 2023-08-04 reviewed by expert panel curation The c.11G>A (p.Trp4Ter) 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.
Color Diagnostics, LLC DBA Color Health RCV001176687 SCV001340728 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 1 of the CDH1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. 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 RCV001176687 SCV002643397 pathogenic Hereditary cancer-predisposing syndrome 2017-04-20 criteria provided, single submitter clinical testing The p.W4* pathogenic mutation (also known as c.11G>A), located in coding exon 1 of the CDH1 gene, results from a G to A substitution at nucleotide position 11. This changes the amino acid from a tryptophan to a stop codon within coding exon 1. 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 RCV001713069 SCV003315335 pathogenic Hereditary diffuse gastric adenocarcinoma 2022-02-19 criteria provided, single submitter clinical testing 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.Trp4*) 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). ClinVar contains an entry for this variant (Variation ID: 918853). For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc. RCV001713069 SCV004044371 pathogenic Hereditary diffuse gastric adenocarcinoma 2023-06-08 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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