Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000553008 | SCV000656017 | uncertain significance | Noonan syndrome 9 | 2024-01-08 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 868 of the SOS2 protein (p.Gly868Ser). This variant is present in population databases (rs751419448, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with SOS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 475746). 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 with a positive predictive value of 80%. 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. |
| Ambry Genetics | RCV003159933 | SCV003911940 | uncertain significance | Cardiovascular phenotype | 2022-11-27 | criteria provided, single submitter | clinical testing | The p.G868S variant (also known as c.2602G>A), located in coding exon 16 of the SOS2 gene, results from a G to A substitution at nucleotide position 2602. The glycine at codon 868 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |