Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001325452 | SCV001516444 | uncertain significance | RASopathy | 2022-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 857 of the SOS1 protein (p.Glu857Asp). 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 not expected to disrupt SOS1 protein function. ClinVar contains an entry for this variant (Variation ID: 40707). This variant has not been reported in the literature in individuals affected with SOS1-related conditions. This variant is present in population databases (rs757460662, gnomAD 0.03%). |
Gene |
RCV003153318 | SCV003842566 | uncertain significance | not provided | 2023-03-13 | criteria provided, single submitter | clinical testing | Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 29493581) |
Ambry Genetics | RCV004018719 | SCV005023031 | uncertain significance | Cardiovascular phenotype | 2023-01-19 | criteria provided, single submitter | clinical testing | The p.E857D variant (also known as c.2571G>C), located in coding exon 16 of the SOS1 gene, results from a G to C substitution at nucleotide position 2571. The glutamic acid at codon 857 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |