ClinVar Miner

Submissions for variant NM_006939.4(SOS2):c.643C>T (p.Arg215Trp)

gnomAD frequency: 0.00001  dbSNP: rs745812984
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
Institute of Human Genetics, University of Leipzig Medical Center RCV001253074 SCV001428596 uncertain significance Noonan syndrome 9 2017-05-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV004035328 SCV003880969 uncertain significance Cardiovascular phenotype 2023-02-28 criteria provided, single submitter clinical testing The c.643C>T (p.R215W) alteration is located in exon 5 (coding exon 5) of the SOS2 gene. This alteration results from a C to T substitution at nucleotide position 643, causing the arginine (R) at amino acid position 215 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003416129 SCV004117049 uncertain significance SOS2-related disorder 2022-08-23 criteria provided, single submitter clinical testing The SOS2 c.643C>T variant is predicted to result in the amino acid substitution p.Arg215Trp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0068% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/14-50655286-G-A). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Labcorp Genetics (formerly Invitae), Labcorp RCV001253074 SCV005715985 uncertain significance Noonan syndrome 9 2024-09-17 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 215 of the SOS2 protein (p.Arg215Trp). This variant is present in population databases (rs745812984, gnomAD 0.007%). 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: 975934). 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 expected to disrupt SOS2 protein function with a positive predictive value of 80%. 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.

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.