Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001056808 | SCV001221272 | pathogenic | RASopathy | 2022-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 428 of the PTPN11 protein (p.Val428Leu). For these reasons, this variant has been classified as Pathogenic. 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: 852241). This missense change has been observed in individual(s) with clinical features of a RASopathy disorder (PMID: 24451042; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). |
Gene |
RCV001788413 | SCV002030909 | likely pathogenic | not provided | 2023-07-07 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30355600, 29493581, 24451042) |
Greenwood Genetic Center Diagnostic Laboratories, |
RCV003514461 | SCV004244518 | likely pathogenic | Noonan syndrome 1 | 2023-11-28 | criteria provided, single submitter | clinical testing | PS4_Supporting, PM2, PM5_Supporting, PP2, PP3 |
Fulgent Genetics, |
RCV005012502 | SCV005632299 | likely pathogenic | Noonan syndrome 1; Juvenile myelomonocytic leukemia; Metachondromatosis; LEOPARD syndrome 1 | 2024-02-15 | criteria provided, single submitter | clinical testing |