Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001015647 | SCV001176504 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-05-28 | criteria provided, single submitter | clinical testing | The c.2480dupA variant, located in coding exon 16 of the CDH1 gene, results from a duplication of A at nucleotide position 2480, causing a translational frameshift with a predicted alternate stop codon (p.Y827*). Frameshifts are typically deleterious in nature, however, this frameshift occurs at the 3' terminus of CDH1, is not expected to trigger nonsense-mediated mRNA decay, and impacts only the last 56 amino acids of the protein. The exact functional impact of these altered amino acids is unknown at this time; however, the deleted region eliminates the catenin-binding domain, which is important for regulating the stability of cadherin mediated cell-cell adhesion (Ishiyama N et al. Cell 2010 Apr; 141(1):117-28). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
Myriad Genetics, |
RCV003336241 | SCV004043683 | pathogenic | Hereditary diffuse gastric adenocarcinoma | 2023-06-15 | 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. |