Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001945587 | SCV002196419 | uncertain significance | RASopathy | 2021-10-14 | 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 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 (ExAC no frequency). This sequence change replaces aspartic acid with glycine at codon 188 of the PTPN11 protein (p.Asp188Gly). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and glycine. |
Fulgent Genetics, |
RCV002479440 | SCV002776094 | uncertain significance | Noonan syndrome 1; Juvenile myelomonocytic leukemia; Metachondromatosis; LEOPARD syndrome 1 | 2021-12-09 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004044150 | SCV005020101 | uncertain significance | Cardiovascular phenotype | 2023-12-11 | criteria provided, single submitter | clinical testing | The p.D188G variant (also known as c.563A>G), located in coding exon 5 of the PTPN11 gene, results from an A to G substitution at nucleotide position 563. The aspartic acid at codon 188 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |