Submissions for variant NM_000546.6(TP53):c.493C>T (p.Gln165Ter)

dbSNP: rs730882001

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000161028	SCV000211749	pathogenic	not provided	2019-05-21	criteria provided, single submitter	clinical testing	Nonsense 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: 31105275, 29452859, 26681312, 29753700, 30824994, 26425688, 30816478, 30720243, 22866089, 29979965)
Ambry Genetics	RCV000219202	SCV000277315	pathogenic	Hereditary cancer-predisposing syndrome	2021-12-13	criteria provided, single submitter	clinical testing	The p.Q165* pathogenic mutation (also known as c.493C>T), located in coding exon 4 of the TP53 gene, results from a C to T substitution at nucleotide position 493. This changes the amino acid from a glutamine to a stop codon within coding exon 4. This variant has been reported in an eleven year old boy diagnosed with medulloblastoma (Waszak SM et al. Lancet Oncol, 2018 06;19:785-798). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Color Diagnostics, LLC DBA Color Health	RCV000219202	SCV000686743	pathogenic	Hereditary cancer-predisposing syndrome	2022-03-15	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 5 of the TP53 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. Experimental studies have shown that this variant results in protein that is non-functional in a human cell proliferation assay (PMID: 29979965). This variant has been reported in individuals affected with breast cancer and medulloblastoma (PMID: 26681312, 29753700, 30287823). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of TP53 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Invitae	RCV000633373	SCV000754595	pathogenic	Li-Fraumeni syndrome	2023-02-03	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln165*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast cancer and medulloblastoma (PMID: 26681312, 29753700). ClinVar contains an entry for this variant (Variation ID: 182930). For these reasons, this variant has been classified as Pathogenic.
Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo	RCV001270262	SCV001450476	pathogenic	Squamous cell carcinoma of the head and neck		criteria provided, single submitter	case-control
Genetics and Molecular Pathology, SA Pathology	RCV002272147	SCV002557031	pathogenic	Familial cancer of breast	2022-05-09	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000219202	SCV002582596	pathogenic	Hereditary cancer-predisposing syndrome	2022-06-18	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002288688	SCV002583158	pathogenic	Li-Fraumeni syndrome 1	2022-06-18	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV002288688	SCV004932170	pathogenic	Li-Fraumeni syndrome 1	2024-02-14	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.
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne	RCV000785484	SCV000924056	pathogenic	Neoplasm of ovary	2018-12-01	no assertion criteria provided	research
Institute of Medical Sciences, Banaras Hindu University	RCV001255634	SCV001432170	pathogenic	Lip and oral cavity carcinoma	2019-04-30	no assertion criteria provided	research