Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001878772 | SCV002134853 | uncertain significance | RASopathy | 2021-03-24 | criteria provided, single submitter | clinical testing | 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. 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 SOS1 protein function. This variant has not been reported in the literature in individuals with SOS1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with serine at codon 885 of the SOS1 protein (p.Arg885Ser). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and serine. |
| Ambry Genetics | RCV003289151 | SCV004002685 | uncertain significance | Cardiovascular phenotype | 2023-03-18 | criteria provided, single submitter | clinical testing | The p.R885S variant (also known as c.2655A>T), located in coding exon 16 of the SOS1 gene, results from an A to T substitution at nucleotide position 2655. The arginine at codon 885 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |