Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003593140 | SCV004285230 | uncertain significance | Noonan syndrome 9 | 2023-03-22 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with SOS2-related conditions. 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 SOS2 protein function. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 1222 of the SOS2 protein (p.Arg1222Leu). |
| Ambry Genetics | RCV004673916 | SCV005170311 | uncertain significance | Cardiovascular phenotype | 2024-06-09 | criteria provided, single submitter | clinical testing | The p.R1222L variant (also known as c.3665G>T), located in coding exon 23 of the SOS2 gene, results from a G to T substitution at nucleotide position 3665. The arginine at codon 1222 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |