Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002051460 | SCV002114385 | uncertain significance | Li-Fraumeni syndrome | 2021-07-03 | criteria provided, single submitter | clinical testing | 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. Experimental studies have shown that this variant affects TP53 protein function (PMID: 12826609, 29979965, 30224644). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TP53 protein function. This variant has been observed in individual(s) with clinical features of Li-Fraumeni syndrome (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with aspartic acid at codon 147 of the TP53 protein (p.Val147Asp). The valine residue is highly conserved and there is a large physicochemical difference between valine and aspartic acid. |
| Baylor Genetics | RCV003464164 | SCV004206278 | uncertain significance | Adrenocortical carcinoma, hereditary | 2023-05-23 | criteria provided, single submitter | clinical testing | |
| Myriad Genetics, |
RCV004038887 | SCV004932680 | likely pathogenic | Li-Fraumeni syndrome 1 | 2024-02-14 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 29979965]. This variant is expected to disrupt protein structure [Myriad internal data]. |