Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002913801 | SCV003254515 | uncertain significance | Noonan syndrome 9 | 2022-05-03 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 1099 of the SOS2 protein (p.Asp1099His). This variant is present in population databases (rs373071240, gnomAD 0.0009%). 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 not 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. |
| Ambry Genetics | RCV004066192 | SCV005025077 | uncertain significance | Cardiovascular phenotype | 2023-12-31 | criteria provided, single submitter | clinical testing | The p.D1099H variant (also known as c.3295G>C), located in coding exon 20 of the SOS2 gene, results from a G to C substitution at nucleotide position 3295. The aspartic acid at codon 1099 is replaced by histidine, 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. |