ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.273G>A (p.Trp91Ter) (rs876660548)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000220815 SCV000278071 pathogenic Hereditary cancer-predisposing syndrome 2016-12-05 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)
GeneDx RCV000657656 SCV000779404 pathogenic not provided 2016-10-26 criteria provided, single submitter clinical testing This variant is denoted TP53 c.273G>A at the cDNA level and p.Trp91Ter (W91X) at the protein level. The substitution creates a nonsense variant, which changes a Tryptophan to a premature stop codon (TGG>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. TP53 Trp91Ter has been reported in two individuals with breast cancer diagnosed at age 30 or younger, one of whom also had a family history of early onset breast cancer, pancreatic cancer, and astrocytoma (Lalloo 2003). This variant is considered pathogenic.
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785284 SCV000923852 pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Invitae RCV000233967 SCV000285181 pathogenic Li-Fraumeni syndrome 2015-12-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 91 (p.Trp91*). It is expected to result in an absent or disrupted protein product. While this particular variant has not been observed in the germline of affected individuals reported in the literature, truncating variants in TP53 are known to be pathogenic (PMID: 20522432). For these reasons, this variant has been classified as Pathogenic.

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