ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.892G>T (p.Glu298Ter)

dbSNP: rs201744589
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen TP53 Variant Curation Expert Panel, ClinGen RCV000559898 SCV001142557 pathogenic Li-Fraumeni syndrome 2019-08-28 reviewed by expert panel curation The p.Glu298* variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1). This variant is absent in the gnomAD cohort (PM2_Supporting; This variant has >10 observations as a somatic hotspot variant in tumors (PM1; v(2)). Additionally, this variant has been reported in at least 2 probands meeting at least Chompret criteria (PS4_Supporting; PMID: 12610779, SCV000278127.5 ). In summary, TP53 c.892G>T; p.Glu298* meets criteria to be classified as pathogenic for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: PVS1, PM2_Supporting, PM1, PS4_Supporting.
Eurofins Ntd Llc (ga) RCV000079204 SCV000111074 pathogenic not provided 2012-09-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV000216964 SCV000278127 pathogenic Hereditary cancer-predisposing syndrome 2022-02-22 criteria provided, single submitter clinical testing The p.E298* pathogenic mutation (also known as c.892G>T), located in coding exon 7 of the TP53 gene, results from a G to T substitution at nucleotide position 892. This changes the amino acid from a glutamic acid to a stop codon within coding exon 7. This alteration was detected in a large Li-Fraumeni kindred consisting of 33 carriers of the alteration and a total of 32 tumors (Wu CC et al. Hum. Genet. 2011 Jun; 129(6):663-73). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Invitae RCV000559898 SCV000629883 pathogenic Li-Fraumeni syndrome 2023-10-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu298*) in the TP53 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of Li-Fraumeni syndrome (PMID: 12610779, 21305319). ClinVar contains an entry for this variant (Variation ID: 93323). For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc. RCV004019532 SCV004933100 pathogenic Li-Fraumeni syndrome 1 2024-02-21 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne RCV000785528 SCV000924100 pathogenic Neoplasm of ovary 2018-12-01 no assertion criteria provided research
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine RCV001257516 SCV001434342 pathogenic Rhabdomyosarcoma 2020-09-01 no assertion criteria provided provider interpretation

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