Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000493802 | SCV000581407 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-11-29 | criteria provided, single submitter | clinical testing | The p.Q1230* pathogenic mutation (also known as c.3688C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 3688. This changes the amino acid from a glutamine to a stop codon within coding exon 15. This variant has been identified in multiple FAP cohorts (Friedl W et al. Hered Cancer Clin Pract, 2005 Sep;3:95-114; Castellsagué E et al. Gastroenterology, 2010 Aug;139:439-47, 447.e1). In addition to the clinical data presented in the literature, 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 | RCV003337246 | SCV003439218 | pathogenic | Familial adenomatous polyposis 1 | 2022-05-07 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the APC protein in which other variant(s) (p.Tyr2645Lysfs*14) have been determined to be pathogenic (PMID: 1316610, 8381579, 9824584, 22135120, 27081525; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 217969). This premature translational stop signal has been observed in individual(s) with familial adenomatous polyposis (PMID: 1316610, 20434453, 20685668). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln1230*) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1614 amino acid(s) of the APC protein. |
| Myriad Genetics, |
RCV003337246 | SCV004044814 | pathogenic | Familial adenomatous polyposis 1 | 2023-05-09 | 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. |
| Color Diagnostics, |
RCV000493802 | SCV004362783 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-03-04 | 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 variant is expected to result in an absent or non-functional protein product. This variant is predicted to escape nonsense-mediated decay and be expressed as a truncated protein. Although functional studies have not been reported, this variant is expected to disrupt the beta-catenin, EB1 binding site, HDLG-binding site, and NLS domains (PMID: 17881494). To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. 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 (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
| Mayo Clinic Laboratories, |
RCV000202019 | SCV000256975 | pathogenic | not provided | no assertion criteria provided | research |