Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000818959 | SCV000959598 | uncertain significance | Noonan syndrome 9 | 2018-11-27 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SOS2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with valine at codon 995 of the SOS2 protein (p.Met995Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine. |
| Ambry Genetics | RCV003307542 | SCV003997557 | uncertain significance | Cardiovascular phenotype | 2023-03-18 | criteria provided, single submitter | clinical testing | The p.M995V variant (also known as c.2983A>G), located in coding exon 19 of the SOS2 gene, results from an A to G substitution at nucleotide position 2983. The methionine at codon 995 is replaced by valine, 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. |