ClinVar Miner

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

dbSNP: rs1597373901
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Total submissions: 4
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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.
Invitae RCV001044605 SCV001208410 pathogenic Li-Fraumeni syndrome 2022-12-06 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 822878). For these reasons, this variant has been classified as Pathogenic. A different variant (c.309C>A) giving rise to the same protein effect has been determined to be pathogenic (PMID: 17224268). This suggests that this variant is also likely to be causative of disease. This variant is not present in population databases (gnomAD no frequency). 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).
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

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