Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000556128 | SCV000629831 | likely benign | Li-Fraumeni syndrome | 2024-09-19 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000578979 | SCV000680591 | uncertain significance | not provided | 2017-09-26 | criteria provided, single submitter | clinical testing | This variant is denoted TP53 c.516T>G at the DNA level. Although this variant is silent at the codinglevel, preserving a Valine at codon 172, it is predicted to cause abnormal splicing through the creation of a new crypticsplice donor site upstream of the natural donor site. However, in the absence of RNA or functional studies, the actualeffect of this variant is unknown. While this variant has not, to our knowledge, been reported as a germline variant ithas been reported as a somatic variant in a neuroblastoma (Hosoi 1994). This variant was not observed in largepopulation cohorts (Lek 2016). The nucleotide which is altered, a thymine (T) at base 516, is not conserved. Based oncurrently available information, it is unclear whether TP53 c.516T>G is a pathogenic or benign variant. We consider itto be a variant of uncertain significance. |
| Ambry Genetics | RCV001023655 | SCV001185566 | likely benign | Hereditary cancer-predisposing syndrome | 2018-01-25 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| All of Us Research Program, |
RCV000556128 | SCV004823790 | uncertain significance | Li-Fraumeni syndrome | 2023-04-03 | criteria provided, single submitter | clinical testing | This synonymous variant causes a T>G nucleotide change in exon 5 of the TP53 gene. Splice site prediction tools indicate that this variant may activate a cryptic donor splice site; however, this prediction has not been confirmed in RNA studies. This variant has not been reported in individuals affected with TP53-related disorders in the literature. This variant has been identified in 3/251338 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |