Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003328297 | SCV001142242 | pathogenic | CDH1-related diffuse gastric and lobular breast cancer syndrome | 2023-08-04 | reviewed by expert panel | curation | The c.337A>T (p.Lys113Ter) 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 |
RCV000220040 | SCV000279542 | pathogenic | not provided | 2015-11-03 | criteria provided, single submitter | clinical testing | This variant is denoted CDH1 c.337A>T at the cDNA level and p.Lys113Ter (K113X) at the protein level. The substitution creates a nonsense variant, which changes a Lysine to a premature stop codon (AAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered pathogenic. |