ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1370C>G (p.Ser457Ter) (rs1060503333)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000470894 SCV000552674 pathogenic Familial adenomatous polyposis 1 2016-05-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 457 (p.Ser457*) of the APC gene. It is expected to result in an absent or disrupted protein product. Truncating variants in APC are known to be pathogenic. This particular truncation has been reported in the literature in individuals with familial adenomatous polyposis (PMID: 20223039, 17411426, 20685668). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000481642 SCV000568270 pathogenic not provided 2017-12-07 criteria provided, single submitter clinical testing This pathogenic variant is denoted APC c.1370C>G at the cDNA level and p.Ser457Ter (S457X) at the protein level. The substitution creates a nonsense variant, which changes a Serine to a premature stop codon (TCA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Ser457Ter has been observed in multiple individuals with Familial Adenomatous Polyposis (FAP) or Attenuated FAP, including at least two related individuals with congenital hypertrophy of the retinal pigment epithelium (CHRPE) (Wallis 1994, Michils 2002, Friedl 2005, Stekrova 2007). Based on currently available evidence, we consider this variant to be pathogenic.
Ambry Genetics RCV000491762 SCV000579843 pathogenic Hereditary cancer-predisposing syndrome 2017-05-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000508095 SCV000602501 pathogenic not specified 2016-09-05 criteria provided, single submitter clinical testing

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.