Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001013219 | SCV001173775 | likely benign | Hereditary cancer-predisposing syndrome | 2019-07-08 | 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. |
Invitae | RCV001057841 | SCV001222356 | uncertain significance | Li-Fraumeni syndrome | 2019-02-11 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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. An experimental study in yeast has shown that this variant impairs the transcriptional transactivation activity of the TP53 protein (PMID: 12826609). This variant has not been reported in the literature in individuals with TP53-related conditions. This sequence change replaces proline with leucine at codon 60 of the TP53 protein (p.Pro60Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. |
Gene |
RCV001776080 | SCV002013045 | uncertain significance | not provided | 2019-06-17 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |