ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.991C>T (p.Gln331Ter)

dbSNP: rs1597359130
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001183200 SCV001348858 pathogenic Hereditary cancer-predisposing syndrome 2020-03-02 criteria provided, single submitter clinical testing This variant is located in the TP53 protein. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been reported for this variant. 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.
Ambry Genetics RCV001183200 SCV003995353 pathogenic Hereditary cancer-predisposing syndrome 2023-05-27 criteria provided, single submitter clinical testing The p.Q331* pathogenic mutation (also known as c.991C>T), located in coding exon 8 of the TP53 gene, results from a C to T substitution at nucleotide position 991. This changes the amino acid from a glutamine to a stop codon within coding exon 8. 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.
Invitae RCV003509657 SCV004296691 pathogenic Li-Fraumeni syndrome 2023-06-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln331*) 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 Li–Fraumeni syndrome (PMID: 25318593). ClinVar contains an entry for this variant (Variation ID: 922893). For these reasons, this variant has been classified as Pathogenic.
Laboratory of Urology, Hospital Clinic de Barcelona RCV003332297 SCV004040608 pathogenic Malignant tumor of urinary bladder no assertion criteria provided research

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.