Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics Munich, |
RCV000995803 | SCV001150156 | pathogenic | Cardiofaciocutaneous syndrome 4 | 2019-06-11 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001851015 | SCV002258771 | likely pathogenic | RASopathy | 2021-08-19 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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 MAP2K2 protein function. ClinVar contains an entry for this variant (Variation ID: 376176). This missense change has been observed in individuals with clinical features of MAP2K2-related conditions (PMID: 25487361; Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with aspartic acid at codon 126 of the MAP2K2 protein (p.Asn126Asp). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and aspartic acid. |
Service de Génétique Moléculaire, |
RCV000824947 | SCV000965982 | likely pathogenic | Cardio-facio-cutaneous syndrome | no assertion criteria provided | clinical testing |