Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002304252 | SCV002591311 | uncertain significance | RASopathy | 2022-07-22 | criteria provided, single submitter | clinical testing | This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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 affected with SOS1-related conditions. This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 436 of the SOS1 protein (p.Asp436His). |
| Ambry Genetics | RCV004990769 | SCV005506157 | uncertain significance | Cardiovascular phenotype | 2024-12-05 | criteria provided, single submitter | clinical testing | The p.D436H variant (also known as c.1306G>C), located in coding exon 10 of the SOS1 gene, results from a G to C substitution at nucleotide position 1306. The aspartic acid at codon 436 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |