Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001991339 | SCV002278143 | uncertain significance | Noonan syndrome 9 | 2024-01-31 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 517 of the SOS2 protein (p.Lys517Thr). This variant is present in population databases (rs367970301, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with SOS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1495360). 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 with a negative predictive value of 80%. 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 | RCV004990549 | SCV005509530 | uncertain significance | Cardiovascular phenotype | 2024-10-07 | criteria provided, single submitter | clinical testing | The p.K517T variant (also known as c.1550A>C), located in coding exon 10 of the SOS2 gene, results from an A to C substitution at nucleotide position 1550. The lysine at codon 517 is replaced by threonine, an amino acid with similar 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. |