Submissions for variant NM_000546.6(TP53):c.298C>T (p.Gln100Ter)

dbSNP: rs1567555994

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Sema4, Sema4	RCV002256497	SCV002530445	likely pathogenic	Hereditary cancer-predisposing syndrome	2020-12-12	criteria provided, single submitter	curation
Ambry Genetics	RCV002256497	SCV002746904	pathogenic	Hereditary cancer-predisposing syndrome	2017-09-07	criteria provided, single submitter	clinical testing	The p.Q100* pathogenic mutation (also known as c.298C>T), located in coding exon 3 of the TP53 gene, results from a C to T substitution at nucleotide position 298. This changes the amino acid from a glutamine to a stop codon within coding exon 3. This mutation has been detected in the germline of a patient with osteosarcoma (Mirabello L et al. J Natl Cancer Inst. 2015 Apr 20;107(7)). 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002535727	SCV003443740	pathogenic	Li-Fraumeni syndrome	2022-07-19	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 634707). This premature translational stop signal has been observed in individual(s) with osteosarcoma (PMID: 25896519). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln100*) 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).
Myriad Genetics, Inc.	RCV004027342	SCV004933558	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.
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV002535727	SCV005689583	likely pathogenic	Li-Fraumeni syndrome	2025-02-04	criteria provided, single submitter	clinical testing	PVS1, PM2_SUP
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne	RCV000785339	SCV000923907	pathogenic	Ovarian neoplasm	2018-12-01	no assertion criteria provided	research
Laboratory of Urology, Hospital Clinic de Barcelona	RCV003332248	SCV004040614	pathogenic	Malignant tumor of urinary bladder		no assertion criteria provided	research