ClinVar Miner

Submissions for variant NM_000038.6(APC):c.288T>G (p.Tyr96Ter)

dbSNP: rs376213437
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000491545 SCV000579865 pathogenic Hereditary cancer-predisposing syndrome 2022-12-29 criteria provided, single submitter clinical testing The p.Y96* pathogenic mutation (also known as c.288T>G), located in coding exon 3 of the APC gene, results from a T to G substitution at nucleotide position 288. This changes the amino acid from a tyrosine to a stop codon within coding exon 3. This mutation was previously observed in a French FAP patient (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 RCV003743628 SCV000647280 pathogenic Familial adenomatous polyposis 1 2023-09-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr96*) in the APC gene. RNA analysis indicates that this premature translational stop signal induces altered splicing and may result in an absent or disrupted protein product. 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 (PMID: 20685668). ClinVar contains an entry for this variant (Variation ID: 217957). Studies have shown that this premature translational stop signal results in activation of a cryptic splice site and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc. RCV002517324 SCV004044820 pathogenic Familial adenomatous polyposis 1 2023-04-25 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003387803 SCV004100106 pathogenic Familial multiple polyposis syndrome 2023-09-25 criteria provided, single submitter clinical testing Variant summary: APC c.288T>G (p.Tyr96X) 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 251468 control chromosomes. c.288T>G has been reported in the literature in individuals affected with Familial Adenomatous Polyposis (Legarde_2010). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 20685668). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Mayo Clinic Laboratories, Mayo Clinic RCV000202141 SCV000256959 pathogenic not provided no assertion criteria provided research

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