ClinVar Miner

Submissions for variant NM_006939.4(SOS2):c.2113G>T (p.Asp705Tyr)

dbSNP: rs1057518079
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000414721 SCV000491468 uncertain significance not specified 2016-03-03 criteria provided, single submitter clinical testing The D705Y variant in the SOS1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The D705Y variant was not observed in approximately 6500 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 D705Y 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 predicts this variant is probably damaging to the protein structure/function. We interpret D705Y as a variant of uncertain significance
Labcorp Genetics (formerly Invitae), Labcorp RCV003754876 SCV004554673 uncertain significance Noonan syndrome 9 2023-06-17 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SOS2 protein function. ClinVar contains an entry for this variant (Variation ID: 372928). This variant has not been reported in the literature in individuals affected with SOS2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 705 of the SOS2 protein (p.Asp705Tyr).

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.