Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003651890 | SCV000552740 | pathogenic | Familial adenomatous polyposis 1 | 2023-10-09 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser1063*) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1781 amino acid(s) of the APC protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with familial adenomatous polyposis (PMID: 9101302, 14961559, 15024739, 15108288, 16134147, 20223039, 20685668, 26446593). ClinVar contains an entry for this variant (Variation ID: 411539). This variant is expected to disrupt the EB1 and HDLG binding sites, which mediate interactions with the cytoskeleton (PMID: 15311282, 17293347). While functional studies have not been performed to directly test the effect on APC protein function, this suggests that disruption of the C-terminal portion of the protein is functionally important. A different truncation (p.Tyr2645Lysfs*14) that lies downstream of this variant has been determined to be pathogenic (PMID: 9824584, 1316610, 27081525, 8381579, 22135120, Invitae). This suggests that deletion of this region of the APC protein is causative of disease. For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV002323747 | SCV002610670 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-11-22 | criteria provided, single submitter | clinical testing | The c.3186_3187delAA pathogenic mutation, located in coding exon 15 of the APC gene, results from a deletion of two nucleotides at nucleotide positions 3186 to 3187, causing a translational frameshift with a predicted alternate stop codon (p.S1063*). This mutation has been reported in multiple FAP families (Gismondi V et al. Hum Mutat, 1997;9:370-3; Vandrovcová J et al. Hum Mutat, 2004 Apr;23:397; Friedl W et al. Hered Cancer Clin Pract, 2005 Sep;3:95-114; Aceto G et al. Hum Mutat, 2005 Oct;26:39; Papp J et al. Fam Cancer, 2016 Jan;15:85-97). 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, |
RCV002526461 | SCV004044811 | pathogenic | Familial adenomatous polyposis 1 | 2023-05-05 | 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. |