ClinVar Miner

Submissions for variant NM_006939.4(SOS2):c.2954T>C (p.Met985Thr)

dbSNP: rs2139550560
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 RCV001973132 SCV002254683 uncertain significance Noonan syndrome 9 2022-06-10 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) performed at Invitae indicates that this missense variant is not expected to disrupt SOS2 protein function. This variant has not been reported in the literature in individuals affected with SOS2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 985 of the SOS2 protein (p.Met985Thr).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004526167 SCV005040439 uncertain significance not specified 2024-03-04 criteria provided, single submitter clinical testing Variant summary: SOS2 c.2954T>C (p.Met985Thr) results in a non-conservative amino acid change located in the Ras guanine-nucleotide exchange factors catalytic domain (IPR001895) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 191880 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2954T>C in individuals affected with Noonan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1469933). Based on the evidence outlined above, the variant was classified as 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.