Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000521009 | SCV000620654 | uncertain significance | not provided | 2017-09-14 | criteria provided, single submitter | clinical testing | The F281S variant in the SOS2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The F281S variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The F281S variant is a non-conservative amino acid substitution, which occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret F281S as a variant of uncertain significance |
| Labcorp Genetics |
RCV003754879 | SCV004554842 | uncertain significance | Noonan syndrome 9 | 2023-06-15 | criteria provided, single submitter | clinical testing | 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 expected to disrupt SOS2 protein function. ClinVar contains an entry for this variant (Variation ID: 451894). This variant has not been reported in the literature in individuals affected with SOS2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 281 of the SOS2 protein (p.Phe281Ser). |