ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.493C>T (p.Gln165Ter) (rs730882001)

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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 RCV000219202 SCV000277315 pathogenic Hereditary cancer-predisposing syndrome 2017-12-19 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)
Color RCV000219202 SCV000686743 pathogenic Hereditary cancer-predisposing syndrome 2017-01-03 criteria provided, single submitter clinical testing
GeneDx RCV000161028 SCV000211749 pathogenic not provided 2018-08-24 criteria provided, single submitter clinical testing This pathogenic variant is denoted TP53 c.493C>T at the cDNA level and p.Gln165Ter (Q165X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. TP53 Gln165Ter has been reported in at least one individual with breast cancer who met TP53 clinical testing criteria and a patient with pediatric-onset medulloblastoma (Susswein 2016, Waszak 2018). 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 RCV000785484 SCV000924056 pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Invitae RCV000633373 SCV000754595 pathogenic Li-Fraumeni syndrome 2017-10-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln165*) 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 an individual affected in a patient with breast cancer (PMID: 26681312).  ClinVar contains an entry for this variant (Variation ID: 182930). 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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