Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003337334 | SCV000814946 | pathogenic | Familial adenomatous polyposis 1 | 2020-02-11 | criteria provided, single submitter | clinical testing | This variant has been reported in individuals affected with familial adenomatous polyposis (PMID: 9476377, 16134147, 20685668). For these reasons, this variant has been classified as Pathogenic. Several different truncations downstream of this variant (p.Ser932*, p.Ala1050Glufs*6, p.Gln1062*) that lie downstream of this variant have been determined to be pathogenic (PMID: 20685668, 23460355, 15771908, 20649969, 8730280, 19531215). This suggests that deletion of this region of the APC protein is causative of disease. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the APC gene (p.Gln767*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 2077 amino acids of the APC protein. |
Institute of Human Genetics, |
RCV002294368 | SCV002587107 | pathogenic | Familial adenomatous polyposis 1 | 2022-10-24 | criteria provided, single submitter | clinical testing | _x000D_ Criteria applied: PVS1, PS4_MOD, PM2_SUP |
Ambry Genetics | RCV002424593 | SCV002731714 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-09-08 | criteria provided, single submitter | clinical testing | The p.Q767* pathogenic mutation (also known as c.2299C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 2299. This changes the amino acid from a glutamine to a stop codon within coding exon 15. This mutation has been identified in multiple individuals with a clinical diagnosis of Familial Adenomatous Polyposis (FAP) (Aceto G et al. Hum. Mutat. 2005 Oct;26:394; Friedl W et al. Hered Cancer Clin Pract. 2005 Sep;3:95-114; Lagarde A et al. J. Med. Genet. 2010 Oct;47:721-2). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation. |
Myriad Genetics, |
RCV003337334 | SCV004045555 | pathogenic | Familial adenomatous polyposis 1 | 2023-05-04 | 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. |