ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.26C>A (p.Ser9Ter)

dbSNP: rs1555509646
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen CDH1 Variant Curation Expert Panel RCV003328471 SCV001943331 pathogenic CDH1-related diffuse gastric and lobular breast cancer syndrome 2023-08-25 reviewed by expert panel curation The c.26C>A (p.Ser9Ter) variant is predicted to result in a premature stop codon in exon 1 that leads to a truncated or absent protein (PVS1, PM5_Supporting). This variant is absent in the gnomAD cohort (PM2_supporting; http://gnomad.broadinstitute.org). Two families meet HDGC phenotypic criteria (PS4_moderate; SCV000947495.1 and internal contributor). In summary, 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 (Variant Interpretation Guidelines Version 3.1): PVS1, PM2_supporting, PS4_moderate, PM5_Supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV000807442 SCV000947495 pathogenic Hereditary diffuse gastric adenocarcinoma 2022-02-28 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with CDH1-related conditions. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 651982). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser9*) 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).
Color Diagnostics, LLC DBA Color Health RCV001191172 SCV001358877 pathogenic Hereditary cancer-predisposing syndrome 2021-06-14 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. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284128 SCV001469752 pathogenic not provided 2019-10-25 criteria provided, single submitter clinical testing The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and not found in general population data.
Myriad Genetics, Inc. RCV000807442 SCV004044589 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.
Baylor Genetics RCV003472394 SCV004210573 likely pathogenic Familial cancer of breast 2021-05-11 criteria provided, single submitter clinical testing

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