ClinVar Miner

Submissions for variant NM_000038.6(APC):c.4700C>G (p.Ser1567Ter)

dbSNP: rs1765745643
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003538631 SCV001407275 pathogenic Familial adenomatous polyposis 1 2023-09-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser1567*) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1277 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: 1316610, 20223039, 20685668). ClinVar contains an entry for this variant (Variation ID: 960996). For these reasons, this variant has been classified as Pathogenic. 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. 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.
Ambry Genetics RCV002339645 SCV002636403 pathogenic Hereditary cancer-predisposing syndrome 2016-10-12 criteria provided, single submitter clinical testing The p.S1567* pathogenic mutation (also known as c.4700C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 4700. This changes the amino acid from a serine 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) (Miyoshi Y et al. Proc. Natl. Acad. Sci. U.S.A. 1992 May;89:4452-6; 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 or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.