ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.772G>T (p.Glu258Ter)

dbSNP: rs121912652
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000565601 SCV000675342 pathogenic Hereditary cancer-predisposing syndrome 2017-03-17 criteria provided, single submitter clinical testing The p.E258* pathogenic mutation (also known as c.772G>T), located in coding exon 6 of the TP53 gene, results from a G to T substitution at nucleotide position 772. This changes the amino acid from a glutamic acid to a stop codon within coding exon 6. 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 RCV000565601 SCV000691642 pathogenic Hereditary cancer-predisposing syndrome 2022-03-15 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 7 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 an individual affected with breast cancer (PMID: 24803582). 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 RCV000565601 SCV002582463 pathogenic Hereditary cancer-predisposing syndrome 2022-06-18 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002289838 SCV002583124 pathogenic Li-Fraumeni syndrome 1 2022-06-18 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003767233 SCV004640849 pathogenic Li-Fraumeni syndrome 2024-01-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu258*) 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 TP53-related conditions (PMID: 32817165). ClinVar contains an entry for this variant (Variation ID: 486557). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne RCV000785351 SCV000923919 pathogenic Ovarian neoplasm 2018-12-01 no assertion criteria provided research

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