Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002927273 | SCV003259797 | uncertain significance | Noonan syndrome 9 | 2023-11-07 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1088 of the SOS2 protein (p.Thr1088Ile). This variant is present in population databases (rs769868981, 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: 2051466). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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 | RCV003170571 | SCV003857639 | uncertain significance | Cardiovascular phenotype | 2023-01-14 | criteria provided, single submitter | clinical testing | The p.T1088I variant (also known as c.3263C>T), located in coding exon 20 of the SOS2 gene, results from a C to T substitution at nucleotide position 3263. The threonine at codon 1088 is replaced by isoleucine, 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. |