Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001887530 | SCV002161418 | uncertain significance | RASopathy | 2022-01-07 | 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. 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 not expected to disrupt PTPN11 protein function. This variant has not been reported in the literature in individuals affected with PTPN11-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 450 of the PTPN11 protein (p.Met450Thr). |
| Ambry Genetics | RCV002386685 | SCV002690304 | uncertain significance | Cardiovascular phenotype | 2018-05-31 | criteria provided, single submitter | clinical testing | The p.M450T variant (also known as c.1349T>C), located in coding exon 11 of the PTPN11 gene, results from a T to C substitution at nucleotide position 1349. The methionine at codon 450 is replaced by threonine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |