Submissions for variant NM_000546.6(TP53):c.159G>A (p.Trp53Ter)

dbSNP: rs1064794618

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000480240	SCV000569586	pathogenic	not provided	2018-08-21	criteria provided, single submitter	clinical testing	This variant is denoted TP53 c.159G>A at the cDNA level and p.Trp53Ter (W53X) at the protein level. The substitution creates a nonsense variant, which changes a Tryptophan to a premature stop codon (TGG>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. TP53 Trp53Ter has been observed in a child with adrenocortical carcinoma (Bougeard 2015). Based on currently available evidence, we consider this variant to be pathogenic.
Ambry Genetics	RCV001012297	SCV001172730	pathogenic	Hereditary cancer-predisposing syndrome	2018-12-20	criteria provided, single submitter	clinical testing	The p.W53* pathogenic mutation (also known as c.159G>A), located in coding exon 3 of the TP53 gene, results from a G to A substitution at nucleotide position 159. This changes the amino acid from a tryptophan to a stop codon within coding exon 3. 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	RCV001236368	SCV001409091	pathogenic	Li-Fraumeni syndrome	2024-04-29	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Trp53*) 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 clinical features of Chompret-Bonaiti (PMID: 35246108). ClinVar contains an entry for this variant (Variation ID: 420659). For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab	RCV001012297	SCV002582626	pathogenic	Hereditary cancer-predisposing syndrome	2022-06-18	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002289632	SCV002583187	pathogenic	Li-Fraumeni syndrome 1	2022-06-18	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV002289632	SCV003804719	pathogenic	Li-Fraumeni syndrome 1	2023-01-20	criteria provided, single submitter	clinical testing	_x000D_ Criteria applied: PVS1, PS4_MOD
Baylor Genetics	RCV003464011	SCV004206260	pathogenic	Adrenocortical carcinoma, hereditary	2023-07-07	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV002289632	SCV004933904	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.