ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.363_364TG[1] (p.Val122fs) (rs587780067)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115720 SCV000149629 pathogenic not provided 2017-10-11 criteria provided, single submitter clinical testing This pathogenic variant is denoted TP53 c.365_366delTG at the cDNA level and p.Val122AspfsX26 (V122DfsX26) at the protein level. The normal sequence, with the bases that are deleted in braces, is TCTG[TG]ACTT. The deletion causes a frameshift, which changes a Valine to an Aspartic Acid at codon 122, and creates a premature stop codon at position 26 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. TP53 c.365_366delTG has been reported in a family with classic Li-Fraumeni syndrome (Wong 2006) and is considered pathogenic.
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785538 SCV000924110 pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Invitae RCV000824056 SCV000964934 pathogenic Li-Fraumeni syndrome 2018-11-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val122Aspfs*26) 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 observed in individuals affected with Li-Fraumeni syndrome (PMID: 16401470, 26681312, 29070607). ClinVar contains an entry for this variant (Variation ID: 127809). 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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