Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genome Diagnostics Laboratory, |
RCV001813669 | SCV002060800 | uncertain significance | Noonan syndrome and Noonan-related syndrome | 2016-12-12 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003539412 | SCV004292330 | uncertain significance | RASopathy | 2023-08-20 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 377 of the MAP2K1 protein (p.Ser377Phe). 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 not expected to disrupt MAP2K1 protein function. ClinVar contains an entry for this variant (Variation ID: 1334254). This variant has not been reported in the literature in individuals affected with MAP2K1-related conditions. This variant is present in population databases (rs371140798, gnomAD 0.002%). |