ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.916C>T (p.Arg306Ter) (rs121913344)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130997 SCV000185920 pathogenic Hereditary cancer-predisposing syndrome 2017-09-18 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
Color RCV000130997 SCV000537679 pathogenic Hereditary cancer-predisposing syndrome 2016-08-05 criteria provided, single submitter clinical testing
Database of Curated Mutations (DoCM) RCV000422102 SCV000505681 likely pathogenic Head and Neck Neoplasms 2015-07-14 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428901 SCV000505682 likely pathogenic Neoplasm of the large intestine 2015-07-14 no assertion criteria provided literature only
GeneDx RCV000356380 SCV000329553 pathogenic not provided 2018-08-14 criteria provided, single submitter clinical testing This pathogenic variant is denoted TP53 c.916C>T at the cDNA level and p.Arg306Ter (R306X) at the protein level. The substitution creates a nonsense variant, which changes an Arginine to a premature stop codon (CGA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been observed in several individuals meeting Li-Fraumeni clinical diagnostic or Chompret testing criteria and has been shown to result in reduced DNA binding activity (Cornelis 1997, Malcikova 2010, Ruijs 2010, Powell 2013, Llovet 2017). Based on currently available evidence, we consider this variant to be pathogenic.
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785333 SCV000923901 pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Invitae RCV000232963 SCV000285215 pathogenic Li-Fraumeni syndrome 2018-12-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg306*) in the TP53 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 the literature in an individual with Li-Fraumeni-like syndrome, an individual with anaplastic rhabdomyosarcoma, and it segregated with TP53-related disease in two families (PMID: 9067756, 24382691, 23255406, 27726232). ClinVar contains an entry for this variant (Variation ID: 142144). Loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). For these reasons, this variant has been classified as Pathogenic.

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