ClinVar Miner

Submissions for variant NM_006939.4(SOS2):c.1273A>G (p.Lys425Glu)

gnomAD frequency: 0.00001  dbSNP: rs372203654
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 RCV000331734 SCV000330689 uncertain significance not provided 2016-07-29 criteria provided, single submitter clinical testing The K425Evariant in the SOS2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The K425E variant was not observed at any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The K425E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret K425E as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001859539 SCV002194278 uncertain significance Noonan syndrome 9 2024-10-21 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 425 of the SOS2 protein (p.Lys425Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SOS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 280746). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt SOS2 protein function with a negative predictive value of 95%. 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.
Genome-Nilou Lab RCV001859539 SCV002763087 uncertain significance Noonan syndrome 9 criteria provided, single submitter clinical testing
Ambry Genetics RCV004992140 SCV005509531 uncertain significance Cardiovascular phenotype 2024-10-25 criteria provided, single submitter clinical testing The p.K425E variant (also known as c.1273A>G), located in coding exon 10 of the SOS2 gene, results from an A to G substitution at nucleotide position 1273. The lysine at codon 425 is replaced by glutamic acid, 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.

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.