Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003328375 | SCV001244356 | pathogenic | CDH1-related diffuse gastric and lobular breast cancer syndrome | 2023-08-25 | reviewed by expert panel | curation | The c.454_460dup p.(Arg154Thrfs) variant is predicted to result in a premature stop codon 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). One family meets HDGC criteria (PS4_supporting; SCV000580703.3). 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_supporting, PM5_Supporting. |
Ambry Genetics | RCV000492486 | SCV000580703 | pathogenic | Hereditary cancer-predisposing syndrome | 2014-03-13 | criteria provided, single submitter | clinical testing | ​The c.454_460dupCAGAAGA mutation, located in coding exon 4 of the CDH1 gene, results from a duplication of the nucleotide sequence CAGAAGA from position 454 through position 460, causing a translational frameshift with a predicted alternate stop codon. Since frameshifts are typically deleterious in nature, this variant is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med 2008;10:294). |
Myriad Genetics, |
RCV003335397 | SCV004045466 | pathogenic | Hereditary diffuse gastric adenocarcinoma | 2023-06-09 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |