ClinVar Miner

Submissions for variant NM_006939.4(SOS2):c.1375A>G (p.Ile459Val)

dbSNP: rs886268693
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001774214 SCV001994751 uncertain significance not provided 2019-03-25 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001882882 SCV002283426 uncertain significance Noonan syndrome 9 2020-11-28 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with SOS2-related conditions. 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 SOS2 protein function. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with valine at codon 459 of the SOS2 protein (p.Ile459Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine.
Genome-Nilou Lab RCV001882882 SCV002763080 uncertain significance Noonan syndrome 9 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV001882882 SCV003822099 uncertain significance Noonan syndrome 9 2023-01-25 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.