Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001984338 | SCV002280443 | uncertain significance | Noonan syndrome 9 | 2023-10-15 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 82 of the SOS2 protein (p.Ile82Val). This variant is present in population databases (rs545263131, gnomAD 0.01%), and has an allele count higher than expected for a pathogenic variant. 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: 1493390). 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. |
| Ambry Genetics | RCV002443015 | SCV002732072 | uncertain significance | Cardiovascular phenotype | 2022-03-04 | criteria provided, single submitter | clinical testing | The p.I82V variant (also known as c.244A>G), located in coding exon 3 of the SOS2 gene, results from an A to G substitution at nucleotide position 244. The isoleucine at codon 82 is replaced by valine, 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. |
| Genome- |
RCV001984338 | SCV002763148 | uncertain significance | Noonan syndrome 9 | criteria provided, single submitter | clinical testing | ||
| Prevention |
RCV003402024 | SCV004104321 | uncertain significance | SOS2-related disorder | 2022-11-04 | criteria provided, single submitter | clinical testing | The SOS2 c.244A>G variant is predicted to result in the amino acid substitution p.Ile82Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/14-50667772-T-C). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |