Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000733128 | SCV000861150 | uncertain significance | not provided | 2018-05-10 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV000733128 | SCV002063069 | uncertain significance | not provided | 2021-12-01 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001868984 | SCV002143718 | uncertain significance | RASopathy | 2023-09-26 | criteria provided, single submitter | clinical testing | 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PTPN11 protein function. 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. ClinVar contains an entry for this variant (Variation ID: 597106). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 382 of the PTPN11 protein (p.Val382Ile). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with PTPN11-related conditions. |
| Ambry Genetics | RCV002458349 | SCV002616367 | uncertain significance | Cardiovascular phenotype | 2021-10-29 | criteria provided, single submitter | clinical testing | The p.V382I variant (also known as c.1144G>A), located in coding exon 10 of the PTPN11 gene, results from a G to A substitution at nucleotide position 1144. The valine at codon 382 is replaced by isoleucine, an amino acid with highly similar properties. This variant was detected in a prenatal specimen referred for genetic testing for Noonan syndrome and related disorders; however, details were limited (Leach NT et al. Genet Med, 2019 02;21:417-425). This amino acid position is not well 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. |
| Fulgent Genetics, |
RCV002499367 | SCV002778219 | uncertain significance | Noonan syndrome 1; Juvenile myelomonocytic leukemia; Metachondromatosis; LEOPARD syndrome 1 | 2022-02-10 | criteria provided, single submitter | clinical testing |