Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mayo Clinic Laboratories, |
RCV006276307 | SCV007132597 | uncertain significance | not provided | 2025-09-27 | criteria provided, single submitter | clinical testing | PP2, PP3, PM2_supporting |
| Fulgent Genetics, |
RCV005012882 | SCV005632275 | uncertain significance | Noonan syndrome 1; Juvenile myelomonocytic leukemia; Metachondromatosis; LEOPARD syndrome 1 | 2024-01-08 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003655420 | SCV004538972 | uncertain significance | RASopathy | 2025-01-08 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 101 of the PTPN11 protein (p.Pro101Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PTPN11-related conditions. ClinVar contains an entry for this variant (Variation ID: 2587732). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt PTPN11 protein function with a positive predictive value of 95%. 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. |
| Ambry Genetics | RCV003339289 | SCV004058033 | uncertain significance | Cardiovascular phenotype | 2025-08-09 | criteria provided, single submitter | clinical testing | The p.P101L variant (also known as c.302C>T), located in coding exon 3 of the PTPN11 gene, results from a C to T substitution at nucleotide position 302. The proline at codon 101 is replaced by leucine, 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. |