ClinVar Miner

Submissions for variant NM_006939.4(SOS2):c.2245A>G (p.Asn749Asp)

gnomAD frequency: 0.00001  dbSNP: rs764992819
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001995744 SCV002275411 uncertain significance Noonan syndrome 9 2024-09-29 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 749 of the SOS2 protein (p.Asn749Asp). This variant is present in population databases (rs764992819, gnomAD 0.002%). 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: 1482671). 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.
Ambry Genetics RCV002425374 SCV002729311 uncertain significance Cardiovascular phenotype 2022-03-19 criteria provided, single submitter clinical testing The p.N749D variant (also known as c.2245A>G), located in coding exon 14 of the SOS2 gene, results from an A to G substitution at nucleotide position 2245. The asparagine at codon 749 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.
Genome-Nilou Lab RCV001995744 SCV002763045 uncertain significance Noonan syndrome 9 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.