ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.1303A>G (p.Lys435Glu)

gnomAD frequency: 0.00001  dbSNP: rs138920742
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001539167 SCV001756911 uncertain significance not provided 2021-01-14 criteria provided, single submitter clinical testing Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002386442 SCV002689865 uncertain significance Cardiovascular phenotype 2022-08-24 criteria provided, single submitter clinical testing The p.K435E variant (also known as c.1303A>G), located in coding exon 10 of the SOS1 gene, results from an A to G substitution at nucleotide position 1303. The lysine at codon 435 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV002468264 SCV002763431 uncertain significance Noonan syndrome 4 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002468263 SCV002763432 uncertain significance Fibromatosis, gingival, 1 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002501873 SCV002805587 uncertain significance Fibromatosis, gingival, 1; Noonan syndrome 4 2021-10-05 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002570639 SCV003444031 uncertain significance RASopathy 2022-05-25 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 435 of the SOS1 protein (p.Lys435Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SOS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1181716). 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 expected to disrupt SOS1 protein function. 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.