Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000523921 | SCV000616918 | uncertain significance | not provided | 2022-02-24 | criteria provided, single submitter | clinical testing | Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Invitae | RCV001343021 | SCV001536976 | uncertain significance | RASopathy | 2022-12-16 | 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. ClinVar contains an entry for this variant (Variation ID: 449117). This variant has not been reported in the literature in individuals affected with PTPN11-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 421 of the PTPN11 protein (p.Arg421Trp). |
| Fulgent Genetics, |
RCV002481692 | SCV002793193 | uncertain significance | Noonan syndrome 1; Juvenile myelomonocytic leukemia; Metachondromatosis; LEOPARD syndrome 1 | 2021-10-28 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003278863 | SCV004007106 | uncertain significance | Cardiovascular phenotype | 2023-05-26 | criteria provided, single submitter | clinical testing | The p.R421W variant (also known as c.1261C>T), located in coding exon 11 of the PTPN11 gene, results from a C to T substitution at nucleotide position 1261. The arginine at codon 421 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. 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. |