Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Myriad Genetics, |
RCV000502557 | SCV004044284 | pathogenic | Familial adenomatous polyposis 1 | 2023-04-28 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
Department of Pathology and Laboratory Medicine, |
RCV000502557 | SCV000591066 | pathogenic | Familial adenomatous polyposis 1 | no assertion criteria provided | clinical testing | The p.Arg405X variant has been previously reported in at least 4 of 2632 proband chromosomes in individuals with FAP (Selected publications: Nagase 1992, Friedl 2005). In addition, this variant has been identified as a frequent mutation in somatic colorectal cancer (Harismendy 2011, Powell 1992). The p.Arg405X variant leads to an amino acid change at position 405 of the polypeptide, and a premature stop codon 49 amino acids downstream. This variant is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the APC gene are an established mechanism of disease causing mutations in FAP. In summary, based on the above information, this variant meets our criteria to be classified as pathogenic. |