Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002349469 | SCV002651573 | uncertain significance | Cardiovascular phenotype | 2021-08-26 | criteria provided, single submitter | clinical testing | The p.I181L variant (also known as c.541A>T), located in coding exon 5 of the SOS2 gene, results from an A to T substitution at nucleotide position 541. The isoleucine at codon 181 is replaced by leucine, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003096730 | SCV003476627 | uncertain significance | Noonan syndrome 9 | 2022-10-01 | 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 not expected to disrupt SOS2 protein function. 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 0.0009%). This sequence change replaces isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 181 of the SOS2 protein (p.Ile181Leu). |