Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000218678 | SCV000275958 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-05-26 | criteria provided, single submitter | clinical testing | The p.S367G variant (also known as c.1099A>G), located in coding exon 9 of the TP53 gene, results from an A to G substitution at nucleotide position 1099. The serine at codon 367 is replaced by glycine, an amino acid with similar properties. This variant is in the tetramerization domain of the TP53 protein and was found to have slighly reduced transactivation capacity when compared to wild type in yeast based functional assays (IARC TP53 database; Kato S et al. Proc Natl Acad Sci USA. 2003 Jul 8;100(14):8424-9). This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 125000 alleles tested) in our clinical cohort. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
| Labcorp Genetics |
RCV001853567 | SCV002300307 | uncertain significance | Li-Fraumeni syndrome | 2021-04-24 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 231953). This sequence change replaces serine with glycine at codon 367 of the TP53 protein (p.Ser367Gly). The serine residue is moderately conserved and there is a small physicochemical difference between serine and glycine. This variant is not present in population databases (ExAC no frequency). Experimental studies have shown that this variant does not substantially affect TP53 protein function (PMID: 12826609, 30224644). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Genome- |
RCV002288872 | SCV002582633 | uncertain significance | Li-Fraumeni syndrome 1 | 2022-06-18 | criteria provided, single submitter | clinical testing | |
| Genome- |
RCV000218678 | SCV002583205 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-18 | criteria provided, single submitter | clinical testing |