Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000214547 | SCV000274039 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2015-02-10 | criteria provided, single submitter | clinical testing | The p.F134C variant (also known as c.401T>G), located in coding exon 4 of the TP53 gene, results from a T to G substitution at nucleotide position 401. The phenylalanine at codon 134 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant is in the DNA binding domain of the TP53 protein and is reported to have loss of transactivation capacity in yeast based assays (IARC TP53 database; Kato S et al. Proc Natl Acad Sci USA. 2003 Jul 8;100(14):8424-9). Structural analysis indicates F134 is a core residue that supports residues responsible for binding DNA. Mutation at this position results in large instability within this region (Bullock AN, Nat. Rev. Cancer 2001 Oct; 1(1):68-76). 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 0.0003% (greater than 250000 alleles tested) in our clinical cohort. This amino acid position is well conserved through mammals. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Mayo Clinic Laboratories, |
RCV000656580 | SCV000778630 | likely pathogenic | not provided | 2013-04-09 | no assertion criteria provided | clinical testing |