ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.309C>G (p.Tyr103Ter)

dbSNP: rs1597373901
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001018609 SCV001179865 pathogenic Hereditary cancer-predisposing syndrome 2019-05-13 criteria provided, single submitter clinical testing The p.Y103* pathogenic mutation (also known as c.309C>G), located in coding exon 3 of the TP53 gene, results from a C to G substitution at nucleotide position 309. This changes the amino acid from a tyrosine to a stop codon within coding exon 3. Studies conducted in human cell lines indicate this alteration is deficient at growth suppression (Kotler E et al. Mol.Cell, 2018 Jul;71:178-190.e8). In addition to the clinical data presented in the literature, 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 RCV001044605 SCV001208410 pathogenic Li-Fraumeni syndrome 2024-06-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr103*) 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: 28681140). ClinVar contains an entry for this variant (Variation ID: 822878). 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.
Genome-Nilou Lab RCV001018609 SCV002582616 pathogenic Hereditary cancer-predisposing syndrome 2022-06-18 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002290537 SCV002583178 pathogenic Li-Fraumeni syndrome 1 2022-06-18 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV002290537 SCV004930645 pathogenic Li-Fraumeni syndrome 1 2024-02-12 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.

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