Submissions for variant NM_000546.6(TP53):c.880del (p.Glu294fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV003196404	SCV003878913	pathogenic	Hereditary cancer-predisposing syndrome	2023-02-21	criteria provided, single submitter	clinical testing	The c.880delG pathogenic mutation, located in coding exon 7 of the TP53 gene, results from a deletion of one nucleotide at nucleotide position 880, causing a translational frameshift with a predicted alternate stop codon (p.E294Sfs*51). This variant has been determined to be the result of a de novo mutation or germline mosaicism in one individual with TP53-associated disease (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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	RCV003779624	SCV004623539	pathogenic	Li-Fraumeni syndrome	2022-10-28	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with TP53-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu294Serfs*51) 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).