ClinVar Miner

Submissions for variant NM_012250.6(RRAS2):c.440G>A (p.Arg147Gln)

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
Labcorp Genetics (formerly Invitae), Labcorp RCV003575991 SCV004369110 uncertain significance not provided 2023-05-01 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 147 of the RRAS2 protein (p.Arg147Gln). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. This variant has not been reported in the literature in individuals affected with RRAS2-related conditions. This variant is present in population databases (rs377321245, gnomAD 0.02%).
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV004786969 SCV005402305 uncertain significance Noonan syndrome 2024-05-07 criteria provided, single submitter clinical testing The RRAS2 c.440G>A (p.Arg147Gln) missense change has a maximum subpopulation frequency of 0.022% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported 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.