Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002333687 | SCV002633309 | uncertain significance | Cardiovascular phenotype | 2022-04-03 | criteria provided, single submitter | clinical testing | The p.N147D variant (also known as c.439A>G), located in coding exon 4 of the SOS2 gene, results from an A to G substitution at nucleotide position 439. The asparagine at codon 147 is replaced by aspartic acid, 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. |
| Labcorp Genetics |
RCV003591938 | SCV004327459 | uncertain significance | Noonan syndrome 9 | 2023-09-29 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 147 of the SOS2 protein (p.Asn147Asp). This variant is not present in population databases (gnomAD no frequency). 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: 1740268). 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. |