ClinVar Miner

Submissions for variant NM_000038.6(APC):c.288T>A (p.Tyr96Ter) (rs376213437)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159585 SCV000209561 pathogenic not provided 2016-04-25 criteria provided, single submitter clinical testing This pathogenic variant is denoted APC c.288T>A at the cDNA level and p.Tyr96Ter (Y96X) at the protein level. The substitution creates a nonsense variant, changing a Tyrosine to a premature stop codon (TAT>TAA). This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been observed in seven Scottish families all presenting with a phenotype suggestive of attenuated-FAP (Ibrahim 2014). Based on current information, we consider this variant to be pathogenic.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000500506 SCV000591022 likely pathogenic Familial adenomatous polyposis 2015-10-02 criteria provided, single submitter clinical testing
Invitae RCV000540671 SCV000647279 pathogenic Familial adenomatous polyposis 1 2018-11-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr96*) 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 an individual with colon polyps (PMID: 26681312) and in 7 families with attenuated familial adenomatous polyposis (AFAP) (PMID: 24549056). ClinVar contains an entry for this variant (Variation ID: 181831). Using a modified segregation analysis based on these 7 families, the relative risk of colon cancer for carriers of this variant was estimated to be 30.78 (95% CI 12.12-78.16) (PMID: 24549056). Two different variants (c.288T>G, c.287dupA) giving rise to the same protein effect observed here (p.Tyr96*) have been reported in individuals affected with or suspected of having familial adenomatous polyposis (FAP) (PMID: 20685668, 23159591). Loss-of-function variants in APC are known to be pathogenic (PMID: 20685668, 17963004). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000159585 SCV000887513 pathogenic not provided 2018-04-11 criteria provided, single submitter clinical testing

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