ClinVar Miner

Submissions for variant NM_005359.5(SMAD4):c.903C>G (p.Tyr301Ter) (rs746084369)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484282 SCV000572364 pathogenic not provided 2018-06-14 criteria provided, single submitter clinical testing This variant is denoted SMAD4 c.903C>G at the cDNA level and p.Tyr301Ter (Y301X) at the protein level. The substitution creates a nonsense variant, which changes a Tyrosine to a premature stop codon (TAC>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, the adjacent variant SMAD4 c.902_903insA, which also results in a premature stop codon at this residue (p.Tyr301Ter), was observed in an individual with multiple juvenile and hyperplastic polyps (Ngeow 2013). Of note, the latter individual also carried a second truncating SMAD4 variant located downstream of Tyr301Ter. We consider SMAD4 Tyr301Ter to be pathogenic.

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