Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003328339 | SCV001437605 | pathogenic | CDH1-related diffuse gastric and lobular breast cancer syndrome | 2023-08-04 | reviewed by expert panel | curation | The c.696_697delTC p.(His233fs) 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 |
RCV000466995 | SCV000545369 | pathogenic | Hereditary diffuse gastric adenocarcinoma | 2021-08-12 | 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. ClinVar contains an entry for this variant (Variation ID: 406615). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.His233Argfs*10) in the CDH1 gene. It is expected to result in an absent or disrupted protein product. |
European Reference Network on Genetic Tumour Risk Syndromes |
RCV000466995 | SCV003926680 | pathogenic | Hereditary diffuse gastric adenocarcinoma | 2022-08-01 | criteria provided, single submitter | clinical testing | PVS1; PS4_Supporting; PM2 (PMID: 30311375) |
Myriad Genetics, |
RCV000466995 | SCV004186599 | pathogenic | Hereditary diffuse gastric adenocarcinoma | 2023-08-25 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |