Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000037625 | SCV000061287 | uncertain significance | not specified | 2014-07-29 | criteria provided, single submitter | clinical testing | The Asp575Gly variant in PTPN11 has not been previously reported in individuals with clinical features of Noonan syndrome or in large population studies. Comput ational prediction tools and evolutionary conservation analysis do not provide s trong support for or against an impact to the protein. In summary, the clinical significance of the Asp575Gly variant is uncertain. |
| Invitae | RCV002513481 | SCV003271090 | uncertain significance | RASopathy | 2021-12-25 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 575 of the PTPN11 protein (p.Asp575Gly). 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. ClinVar contains an entry for this variant (Variation ID: 44601). 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). |