Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002727011 | SCV003007792 | uncertain significance | Noonan syndrome 9 | 2022-04-25 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with SOS2-related conditions. 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. This variant is present in population databases (rs202201300, gnomAD 0.0009%). This sequence change replaces leucine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 548 of the SOS2 protein (p.Leu548Ile). |
| Ambry Genetics | RCV003308245 | SCV003996303 | uncertain significance | Cardiovascular phenotype | 2023-03-26 | criteria provided, single submitter | clinical testing | The p.L548I variant (also known as c.1642C>A), located in coding exon 10 of the SOS2 gene, results from a C to A substitution at nucleotide position 1642. The leucine at codon 548 is replaced by isoleucine, an amino acid with highly 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. |