ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3183_3187del (p.Lys1061_Gln1062insTer) (rs587779352)

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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162768 SCV000213245 pathogenic Hereditary cancer-predisposing syndrome 2018-01-25 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
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000077987 SCV000226392 pathogenic not provided 2013-08-22 criteria provided, single submitter clinical testing
Invitae RCV000144562 SCV000253730 pathogenic Familial adenomatous polyposis 1 2018-12-16 criteria provided, single submitter clinical testing This sequence change deletes 5 nucleotides from exon 16 of the APC mRNA (c.3183_3187delACAAA), causing a frameshift at codon 1061. This creates a premature translational stop signal in the last exon of the APC mRNA (p.Gln1062*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 1782 amino acids (~63%) of the APC protein. Loss-of-function variants in APC are known to be pathogenic. This particular variant has been reported in the literature in many individuals affected with familial adenomatous polyposis (PMID: 1316610, 8162022, 15771908). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000077987 SCV000293390 pathogenic not provided 2018-11-06 criteria provided, single submitter clinical testing This deletion of five nucleotides is denoted APC c.3183_3187delACAAA at the cDNA level and p.Gln1062Ter (Q1062X) at the protein level. The normal sequence, with the bases that are deleted in brackets, is TAAA[delACAAA]GTGA. The deletion creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAA>TGA), and is predicted to cause loss of normal protein function through protein truncation. Even though this frameshift occurs near the end of the gene and nonsense-mediated decay is not expected to occur, it is significant since the last 1782 amino acids are no longer translated. APC c.3183_3187delACAAA has been observed in multiple individuals with Familial Adenomatous Polyposis (Aceto 2005, Plawski 2008, Gomez-Fernandez 2009, Rivera 2011, Papp 2015, Liu 2016, Zhang 2016, Khan 2017). This variant is considered pathogenic.
Counsyl RCV000144562 SCV000488338 pathogenic Familial adenomatous polyposis 1 2016-03-03 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000502016 SCV000591132 pathogenic Familial adenomatous polyposis criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000077987 SCV000600078 pathogenic not provided 2017-04-03 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000502016 SCV000694026 pathogenic Familial adenomatous polyposis 2016-07-15 criteria provided, single submitter clinical testing Variant summary: The APC c.3183_3187delACAAA (p.Gln1062fs) variant results in a premature termination codon, predicted to cause a truncated or absent APC protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant was absent in 120668 control chromosomes, but has been cited in numerous FAP patients reported in the literature and is considered a common pathogenic variant. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic/causal. Taken together, this variant is classified as Pathogenic.
National Molecular Genetics Centre of Cancer Research,N.N. Alexandrov National Cancer Centre of Belarus RCV000144562 SCV000778310 pathogenic Familial adenomatous polyposis 1 2018-05-28 criteria provided, single submitter clinical testing This sequence change (c.3183_3187delACAAA) creates a stop codon (p.Gln1062*) in exon 16 of the APC mRNA.
Center for Human Genetics, Inc RCV000502016 SCV000781075 pathogenic Familial adenomatous polyposis 2016-11-01 criteria provided, single submitter clinical testing
GeneKor MSA RCV000077987 SCV000821693 pathogenic not provided 2018-08-01 criteria provided, single submitter clinical testing
Mendelics RCV000144562 SCV000838100 pathogenic Familial adenomatous polyposis 1 2018-07-02 criteria provided, single submitter clinical testing
Clinical Genomics Lab,St. Jude Children's Research Hospital RCV000722012 SCV000853185 pathogenic Craniopharyngioma 2016-02-29 criteria provided, single submitter clinical testing This is a frameshift mutation in which 5 nucleotides are deleted between coding positions 3183 and 3187 and is predicted to shift the reading frame at codon 1061.
Color RCV000162768 SCV000905975 pathogenic Hereditary cancer-predisposing syndrome 2018-03-09 criteria provided, single submitter clinical testing
Pathway Genomics RCV000144562 SCV000189853 pathogenic Familial adenomatous polyposis 1 2014-07-24 no assertion criteria provided clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000077987 SCV000256968 pathogenic not provided no assertion criteria provided clinical testing

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