ClinVar Miner

Submissions for variant NM_006939.4(SOS2):c.1264G>A (p.Glu422Lys)

gnomAD frequency: 0.00003  dbSNP: rs375244948
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
Labcorp Genetics (formerly Invitae), Labcorp RCV001305509 SCV001494847 likely benign Noonan syndrome 9 2025-01-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV002447309 SCV002676308 uncertain significance Cardiovascular phenotype 2021-06-23 criteria provided, single submitter clinical testing The p.E422K variant (also known as c.1264G>A), located in coding exon 10 of the SOS2 gene, results from a G to A substitution at nucleotide position 1264. The glutamic acid at codon 422 is replaced by lysine, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV001305509 SCV002763089 uncertain significance Noonan syndrome 9 criteria provided, single submitter clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV001305509 SCV005689320 uncertain significance Noonan syndrome 9 2025-02-05 criteria provided, single submitter clinical testing The SOS2 c.1264G>A (p.Glu422Lys) missense change has a maximum subpopulation frequency of 0.004% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). This variant occurs in a gene where missense variants are more likely to be damaging based on methods described by Lek et al. (PMID: 27535533). The in silico tool REVEL predicts a deleterious effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in the literature in individuals with Noonan syndrome. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.

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.