Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003328243 | SCV001142252 | pathogenic | CDH1-related diffuse gastric and lobular breast cancer syndrome | 2023-08-04 | reviewed by expert panel | curation | The c.707C>A (p.Ser236Ter) 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. |
Gene |
RCV000160385 | SCV000210901 | pathogenic | not provided | 2014-04-19 | criteria provided, single submitter | clinical testing | This pathogenic variant is denoted CDH1 c.707C>A at the cDNA level and p.Ser236Ter (S236X) at the protein level. The substitution creates a nonsense variant, changing a Serine to a premature stop codon (TCA>TAA). This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not been previously reported to our knowledge, it is considered pathogenic. |