ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.636del (p.Arg213fs)

dbSNP: rs864309495
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen TP53 Variant Curation Expert Panel, ClinGen RCV001527089 SCV001737928 pathogenic Li-Fraumeni syndrome 1 2020-09-04 reviewed by expert panel curation The p.R213fs 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; http://gnomad.broadinstitute.org). This variant has been reported in 2 probands meeting Chompret criteria (PS4_Supporting; PMID: 11370630, NIH). In summary, TP53 c.636del (p.R213fs) 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, PS4_Supporting.
GeneDx RCV001576599 SCV001803822 pathogenic not provided 2020-10-26 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 11370630, 30720243)
Invitae RCV001853261 SCV002221571 pathogenic Li-Fraumeni syndrome 2021-11-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg213Aspfs*34) 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). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 218342). This premature translational stop signal has been observed in individual(s) with Li-Fraumeni syndrome (PMID: 11370630). This variant is not present in population databases (gnomAD no frequency).
Ambry Genetics RCV002363022 SCV002658063 pathogenic Hereditary cancer-predisposing syndrome 2020-03-04 criteria provided, single submitter clinical testing The c.636delT pathogenic mutation, located in coding exon 5 of the TP53 gene, results from a deletion of one nucleotide at nucleotide position 636, causing a translational frameshift with a predicted alternate stop codon (p.R213Dfs*34). This mutation has previously been reported in a family from a cohort of families fulfilling Chompret critiera and families suggestive of Li Fraumeni syndrome (Bougeard et al. 2008 J Med Genet 45(8):535-8 Supplementary Data). 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.
Institute of Human Genetics, University of Leipzig Medical Center RCV001527089 SCV004027693 pathogenic Li-Fraumeni syndrome 1 2023-06-15 criteria provided, single submitter clinical testing Criteria applied: PVS1,PS4_MOD,PM2_SUP
McDonnell Genome Institute, Washington University in St. Louis RCV000202592 SCV000257335 pathogenic Acute megakaryoblastic leukemia; Mediastinal germ cell tumor 2015-10-22 no assertion criteria provided research

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