Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002938281 | SCV003264949 | likely pathogenic | RASopathy | 2023-05-22 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 112 of the MAP2K2 protein (p.Arg112Gln). 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. This variant disrupts the p.Arg112 amino acid residue in MAP2K2. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 MAP2K2 protein function. ClinVar contains an entry for this variant (Variation ID: 2055907). This variant has not been reported in the literature in individuals affected with MAP2K2-related conditions. This variant is not present in population databases (gnomAD no frequency). |
| Fulgent Genetics, |
RCV005019475 | SCV005648275 | uncertain significance | Cardiofaciocutaneous syndrome 4 | 2024-01-30 | criteria provided, single submitter | clinical testing |