Submissions for variant NM_000546.6(TP53):c.321C>G (p.Tyr107Ter)

dbSNP: rs770776262

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001386369	SCV001586561	pathogenic	Li-Fraumeni syndrome	2020-05-13	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). Different variants, giving rise to the same protein effect observed here (p.Tyr107*), have been observed in individuals affected with breast cancer, and are determined to be pathogenic (PMID: 25877891, 25927356). This suggests that this variant is also likely to be causative of disease. This variant has not been reported in the literature in individuals with TP53-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr107*) in the TP53 gene. It is expected to result in an absent or disrupted protein product.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV003321833	SCV004026094	pathogenic	not provided	2022-05-24	criteria provided, single submitter	clinical testing	PVS1, PS1, PM2_SUP, PP2
Myriad Genetics, Inc.	RCV004037681	SCV004932799	pathogenic	Li-Fraumeni syndrome 1	2024-02-12	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.