Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004261256 | SCV003885501 | uncertain significance | Cardiovascular phenotype | 2024-06-24 | criteria provided, single submitter | clinical testing | The p.R574H variant (also known as c.1721G>A), located in coding exon 10 of the SOS2 gene, results from a G to A substitution at nucleotide position 1721. The arginine at codon 574 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Labcorp Genetics |
RCV003755018 | SCV004518512 | uncertain significance | Noonan syndrome 9 | 2023-08-28 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 2468841). This variant has not been reported in the literature in individuals affected with SOS2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 574 of the SOS2 protein (p.Arg574His). |