ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3670_3671dup (p.Asn1224fs)

dbSNP: rs1561586671
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
Labcorp Genetics (formerly Invitae), Labcorp RCV004564440 SCV000834794 pathogenic Familial adenomatous polyposis 1 2018-07-16 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. A different truncation downstream of this variant (p.Glu1309Aspfs*4) has been determined to be pathogenic (PMID: 20223039, 1316610, 23159591, 24664542). This suggests that deletion of this region of the APC protein is causative of disease. This variant has not been reported in the literature in individuals with APC-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the APC gene (p.Asn1224Lysfs*42). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1620 amino acids of the APC protein.
Mayo Clinic Laboratories, Mayo Clinic RCV002251750 SCV002522535 likely pathogenic not provided 2021-06-18 criteria provided, single submitter clinical testing PM2, PVS1_strong
Ambry Genetics RCV002458314 SCV002613443 pathogenic Hereditary cancer-predisposing syndrome 2022-09-09 criteria provided, single submitter clinical testing The c.3670_3671dupAA pathogenic mutation, located in coding exon 15 of the APC gene, results from a duplication of AA at nucleotide position 3670, causing a translational frameshift with a predicted alternate stop codon (p.N1224Kfs*42). This alteration occurs at the 3' terminus of the APC gene, and is not expected to trigger nonsense mediated mRNA decay, however, premature stop codons are typically deleterious in nature and structural analysis suggests this deletion removes a known motif (Thr2841-Ser2842-Val2843) needed for protein binding involved in regulation of protein function (Slep KC et al, PLoS ONE 2012; 7(11):e50097; Zhang Z et al, PLoS ONE 2011; 6(8):e23507). This alteration has been observed in at least one individual with a personal and/or family history that is consistent with APC-related disease (Ambry internal data). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc. RCV004564440 SCV004044584 pathogenic Familial adenomatous polyposis 1 2023-05-09 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.