ClinVar Miner

Submissions for variant NM_000038.6(APC):c.476dup (p.Tyr159Ter)

dbSNP: rs878853451
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000229992 SCV000282764 pathogenic Familial adenomatous polyposis 1 2024-10-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr159*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with familial adenomatous polyposis (FAP) (PMID: 8956059, 20223039, 20685668). ClinVar contains an entry for this variant (Variation ID: 236607). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000229992 SCV000488330 likely pathogenic Familial adenomatous polyposis 1 2016-03-01 criteria provided, single submitter clinical testing
GeneDx RCV000486696 SCV000564559 pathogenic not provided 2023-01-25 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28944238, 20223039, 15951963, 20685668, 23159591, 27623068, 8956059)
Mayo Clinic Laboratories, Mayo Clinic RCV000486696 SCV001714739 pathogenic not provided 2020-12-18 criteria provided, single submitter clinical testing PVS1, PM2, PP4
Ambry Genetics RCV002338700 SCV002638664 pathogenic Hereditary cancer-predisposing syndrome 2023-01-20 criteria provided, single submitter clinical testing The c.476dupA pathogenic mutation, located in coding exon 4 of the APC gene, results from a duplication of A at nucleotide position 476, causing a translational frameshift with a predicted alternate stop codon (p.Y159*). This variant was identified in 1/863 colonic polyposis patients from a French cohort (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.
Myriad Genetics, Inc. RCV000229992 SCV004017792 pathogenic Familial adenomatous polyposis 1 2023-02-16 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Baylor Genetics RCV000229992 SCV004205460 pathogenic Familial adenomatous polyposis 1 2023-11-18 criteria provided, single submitter clinical testing

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