ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1886dup (p.Leu629fs)

dbSNP: rs863224817
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 RCV000195881 SCV000255230 pathogenic Familial adenomatous polyposis 1 2015-04-29 criteria provided, single submitter clinical testing This sequence change inserts 1 nucleotide in exon 15 of the APC mRNA (c.1886dupT), causing a frameshift at codon 629. This creates a premature translational stop signal (p.Leu629Phefs*5) and is expected to result in an absent or disrupted protein product. Truncating variants in APC are known to be pathogenic. This particular truncation was reported in individuals affected with familial adenomatous polyposis (PMID: 20223039, 20685668), and has been observed in affected patients in the Universal Mutation Database (PMID: 24599579). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000493455 SCV000581415 pathogenic Hereditary cancer-predisposing syndrome 2019-09-10 criteria provided, single submitter clinical testing The c.1886dupT pathogenic mutation, located in coding exon 14 of the APC gene, results from a duplication of T at nucleotide position 1886, causing a translational frameshift with a predicted alternate stop codon (p.L629Ffs*5). This alteration was identified in 1/1164 unrelated German index patients with a clinical diagnosis of familial adenomatous polyposis (FAP) or attenuated familial adenomatous polyposis (AFAP) (Friedl W et al. Hered Cancer Clin Pract, 2005 Sep;3:95-114). This alteration was also identified in 2/934 French patients with FAP (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.
Invitae RCV000195881 SCV002238486 pathogenic Familial adenomatous polyposis 1 2023-03-07 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 216839). This premature translational stop signal has been observed in individual(s) with familial adenomatous polyposis (PMID: 1324223, 20223039, 20685668, 24599579). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu629Phefs*5) in the APC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668).
Myriad Genetics, Inc. RCV000195881 SCV004045650 pathogenic Familial adenomatous polyposis 1 2023-05-03 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

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.