ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.919+2T>G

dbSNP: rs1131691016
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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV006273840 SCV007129820 oncogenic Neoplasm 2025-12-29 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV002289666 SCV004932223 likely pathogenic Li-Fraumeni syndrome 1 2024-02-21 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function.
Genome-Nilou Lab RCV002289666 SCV002583107 pathogenic Li-Fraumeni syndrome 1 2022-06-18 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000492618 SCV002582445 pathogenic Hereditary cancer-predisposing syndrome 2022-06-18 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000808655 SCV000948769 pathogenic Li-Fraumeni syndrome 2021-08-28 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 428877). Disruption of this splice site has been observed in individual(s) with Li-Fraumeni syndrome (PMID: 29070607). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 8 of the TP53 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432).
Ambry Genetics RCV000492618 SCV000581110 pathogenic Hereditary cancer-predisposing syndrome 2026-02-18 criteria provided, single submitter clinical testing The c.919+2T>G intronic pathogenic mutation results from a T to G substitution 2 nucleotides after coding exon 7 in the TP53 gene. This pathogenic mutation has been detected as a de novo finding in an individual with metastatic early onset breast cancer (Ambry internal data). In silico splice site analysis predicts that this alteration will weaken the native splice donor site, and RNA evidence supports this prediction (Ambry internal data). Based on the supporting evidence, this variant is interpreted as a disease-causing mutation.
Dr. Peter K. Rogan Lab, Western University RCV005899764 SCV006897716 not provided Malignant tumor of esophagus no classification provided in vitro
Dr. Peter K. Rogan Lab, Western University RCV005899764 SCV006897715 not provided Malignant tumor of esophagus no classification provided in vitro
Dr. Peter K. Rogan Lab, Western University RCV005899765 SCV006897714 not provided Ovarian serous cystadenocarcinoma no classification provided in vitro
Dr. Peter K. Rogan Lab, Western University RCV005899762 SCV006897713 not provided Colon adenocarcinoma no classification provided in vitro
Dr. Peter K. Rogan Lab, Western University RCV005899763 SCV006897712 not provided Squamous cell carcinoma of the head and neck no classification provided in vitro
Dr. Peter K. Rogan Lab, Western University RCV005899763 SCV006897710 not provided Squamous cell carcinoma of the head and neck no classification provided in vitro
MutSpliceDB: a database of splice sites variants effects on splicing, NIH RCV001542803 SCV001761179 not provided not provided no classification provided in vivo

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