Total submissions: 4
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- |
RCV001018609 | SCV002582616 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-06-18 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV002290537 | SCV002583178 | pathogenic | Li-Fraumeni syndrome 1 | 2022-06-18 | criteria provided, single submitter | clinical testing |