ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.626_627del (p.Arg209fs) (rs1057517840)

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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 RCV000492427 SCV000581172 pathogenic Hereditary cancer-predisposing syndrome 2016-05-04 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 RCV000414120 SCV000490857 pathogenic not provided 2018-08-09 criteria provided, single submitter clinical testing This deletion of 2 nucleotides in TP53 is denoted c.626_627delGA at the cDNA level andp.Arg209LysfsX6 (R209KfsX6) at the protein level. The normal sequence, with the bases that are deleted in brackets,is GACA{GA}AACA. The deletion causes a frameshift, which changes an Arginine to a Lysine at codon 209 in exon 6,and creates a premature stop codon at position 6 of the new reading frame. This pathogenic variant is predicted tocause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. TP53c.626_627delGA has been reported in a child with embryonal rhabdomyosarcoma and subsequent myelodysplasticsyndrome (Felix 1996) and is considered to be a pathogenic variant.
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785270 SCV000923838 pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Invitae RCV000539085 SCV000629847 pathogenic Li-Fraumeni syndrome 2018-11-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg209Lysfs*6) 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 as a germline variant in an individual affected with embryonal rhabdomyosarcoma and therapy-related myelodysplastic syndrome (PMID: 8639798). ClinVar contains an entry for this variant (Variation ID: 372539). 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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