Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000703310 | SCV000832206 | uncertain significance | Noonan syndrome 9 | 2023-10-09 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 1135 of the SOS2 protein (p.Ser1135Gly). This variant is present in population databases (rs375478974, gnomAD 0.0008%). 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: 579913). 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. |
St. |
RCV000703310 | SCV002032287 | uncertain significance | Noonan syndrome 9 | 2023-05-11 | criteria provided, single submitter | clinical testing | The SOS2 c.3403A>G (p.Ser1135Gly) missense change is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). This variant occurs in a gene where missense variants are a common mechanism of disease. The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with Noonan syndrome. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |
Ambry Genetics | RCV002458295 | SCV002614973 | uncertain significance | Cardiovascular phenotype | 2021-08-19 | criteria provided, single submitter | clinical testing | The p.S1135G variant (also known as c.3403A>G), located in coding exon 22 of the SOS2 gene, results from an A to G substitution at nucleotide position 3403. The serine at codon 1135 is replaced by glycine, 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. |
Genome- |
RCV000703310 | SCV002762998 | uncertain significance | Noonan syndrome 9 | criteria provided, single submitter | clinical testing |