Submissions for variant NM_000546.6(TP53):c.52del (p.Thr18fs)

dbSNP: rs876658627

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000213243	SCV000274136	pathogenic	Hereditary cancer-predisposing syndrome	2015-03-02	criteria provided, single submitter	clinical testing	The c.52delA pathogenic mutation, located in coding exon 1 of the TP53 gene, results from a deletion of one nucleotide at nucleotide position 52, causing a translational frameshift with a predicted alternate stop codon. Since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Color Diagnostics, LLC DBA Color Health	RCV000213243	SCV000691599	pathogenic	Hereditary cancer-predisposing syndrome	2022-03-11	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 2 of the TP53 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. 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.
Genome-Nilou Lab	RCV000213243	SCV002582629	pathogenic	Hereditary cancer-predisposing syndrome	2022-06-18	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002288855	SCV002583191	pathogenic	Li-Fraumeni syndrome 1	2022-06-18	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV005090081	SCV005815897	pathogenic	Li-Fraumeni syndrome	2024-04-03	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Thr18Hisfs*26) 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 synchronous malignancies and clinical features of Li Fraumeni syndrome (PMID: 29737433). ClinVar contains an entry for this variant (Variation ID: 230550). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV005090081	SCV006071940	pathogenic	Li-Fraumeni syndrome	2025-03-21	criteria provided, single submitter	clinical testing	Variant summary: TP53 c.52delA (p.Thr18HisfsX26) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 250526 control chromosomes. c.52delA has been reported in the literature in individuals affected with Li-Fraumeni Syndrome (example: Rana_2019). The following publication has been ascertained in the context of this evaluation (PMID: 31105275). ClinVar contains an entry for this variant (Variation ID: 230550). Based on the evidence outlined above, the variant was classified as pathogenic.