ClinVar Miner

Submissions for variant NM_000038.6(APC):c.426_427del (p.Leu143fs) (rs587782557)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 10
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131775 SCV000186822 pathogenic Hereditary cancer-predisposing syndrome 2018-02-12 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),Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
GeneDx RCV000202026 SCV000209475 pathogenic not provided 2016-12-27 criteria provided, single submitter clinical testing This deletion of 2 nucleotides in APC is denoted c.426_427delAT at the cDNA level and p.Leu143AlafsX4 (L143AfsX4) at the protein level. The normal sequence, with the bases that are deleted in braces, is gGTC{AT}TGCT, where the capital letters are exonic and lowercase letter is intronic. The deletion causes a frameshift, which changes a Leucine to an Alanine at codon 143, and creates a premature stop codon at position 4 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. APC c.426_427delAT has been observed in association with classic or attenuated Familial Adenomatous Polyposis and has been described as an American founder pathogenic variant (Spirio 1993, Friedl 2005, Neklason 2008). Based on the currently available evidence, we consider this variant to be pathogenic.
Invitae RCV000144571 SCV000253733 pathogenic Familial adenomatous polyposis 1 2018-12-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu143Alafs*4) in the APC gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in individuals and families affected with attenuated familial adenomatous polyposis (PMID: 18063416, 8252630, 15300576, 23159591, 11960572). It has also been observed in individuals affected with pilomatrixomas (PMID: 22150579). ClinVar contains an entry for this variant (Variation ID: 142574). Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). For these reasons, this variant has been classified as Pathogenic.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000504124 SCV000591030 pathogenic Familial adenomatous polyposis 2014-11-06 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000202026 SCV000600097 pathogenic not provided 2016-03-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000506761 SCV000602528 pathogenic not specified 2017-02-08 criteria provided, single submitter clinical testing
Color RCV000131775 SCV000905872 pathogenic Hereditary cancer-predisposing syndrome 2017-11-30 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000504124 SCV000918439 pathogenic Familial adenomatous polyposis 2018-05-01 criteria provided, single submitter clinical testing Variant summary: APC c.426_427delAT (p.Leu143AlafsX4) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 119962 control chromosomes. c.426_427delAT has been reported in the literature as an American founder mutation in several large kindreds with Familial Adenomatous Polyposis. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and all classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Pathway Genomics RCV000144571 SCV000189867 pathogenic Familial adenomatous polyposis 1 2014-07-24 no assertion criteria provided clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202026 SCV000256995 pathogenic not provided no assertion criteria provided 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.