ClinVar Miner

Submissions for variant NM_005633.3(SOS1):c.3322G>A (p.Asp1108Asn) (rs199856844)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000234075 SCV000288965 uncertain significance Rasopathy 2018-08-11 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 1108 of the SOS1 protein (p.Asp1108Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs199856844, ExAC 0.03%). This variant has not been reported in the literature in individuals with SOS1-related disease. ClinVar contains an entry for this variant (Variation ID: 240197). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
GeneDx RCV000333119 SCV000330895 uncertain significance not provided 2019-01-14 criteria provided, single submitter clinical testing The D1108N variant in the SOS1 gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The 1000 Genomes Project Consortium reports it was observed in 2/694 (0.29%) alleles from individuals of mixed American background, indicating it may be a rare variant in this population. D1108N is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved; however, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000825457 SCV000966758 uncertain significance not specified 2018-05-02 criteria provided, single submitter clinical testing The p.Asp1108Asn variant has not been previously reported in individuals with cl inical features of a RASopathy disorder, but has been reported in ClinVar (Varia tion ID: 238770). This variant has been identified in 4/33558 Latino chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; d bSNP rs199856844). Please note that for diseases with clinical variability, redu ced penetrance, or recessive inheritance, pathogenic variants may be present at a low frequency in the general population. Computational prediction tools and co nservation analysis suggest that the p.Asp1108Asn variant may not impact the pro tein, though this information is not predictive enough to rule out pathogenicity . In summary, the clinical significance of the p.Asp1108Asn variant is uncertain . ACMG/AMP Criteria applied: BP4.

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.