Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000985300 | SCV001133331 | pathogenic | not provided | 2018-09-21 | criteria provided, single submitter | clinical testing | The variant creates a premature nonsense codon, and is therefore predicted to significantly disrupt the protein structure. Found in at least one symptomatic patient, and not found in general population data. |
| Color Diagnostics, |
RCV001180269 | SCV001345151 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-07-18 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 16 of the APC gene, creating a premature translation stop signal in the last coding exon. This mutant transcript is predicted to be expressed as a truncated protein. Although functional studies have not been performed, this variant is expected to disrupt many important functional domains including beta-catenin binding domain, basic domain, EB1 binding domain, and Human Disc Large (HDLG) binding domain (PMID: 17881494). Many truncating variants occurring downstream of this variant are known to be disease-causing in Clinvar. This variant has been reported in a Chilean family affected with familial adenomatous polyposis (PMID: 17963004). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of APC function is a known mechanism of disease. Based on available evidence, this variant is classified as Pathogenic. |
| Ambry Genetics | RCV001180269 | SCV002620321 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-11-19 | criteria provided, single submitter | clinical testing | The p.E1306* pathogenic mutation (also known as c.3916G>T), located in coding exon 15 of the APC gene, results from a G to T substitution at nucleotide position 3916. This changes the amino acid from a glutamic acid to a stop codon within coding exon 15. This variant was detected in 1/24 Chilean families with familial adenomatous polyposis (FAP) (De la Fuente MK et al. Dis Colon Rectum, 2007 Dec;50:2142-8). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Invitae | RCV003535701 | SCV004292816 | pathogenic | Familial adenomatous polyposis 1 | 2023-11-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu1306*) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1538 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: 17963004). ClinVar contains an entry for this variant (Variation ID: 376059). 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. |
| Database of Curated Mutations |
RCV000443324 | SCV000504999 | likely pathogenic | Neoplasm of the large intestine | 2015-07-14 | no assertion criteria provided | literature only |