ClinVar Miner

Submissions for variant NM_006939.4(SOS2):c.1175A>G (p.Tyr392Cys)

dbSNP: rs1085307558
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489878 SCV000576719 uncertain significance not provided 2017-04-20 criteria provided, single submitter clinical testing The Y392C variant in the SOS2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The Y392C variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The Y392C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved and not within a known functional or structural domain. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret Y392C as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV003754878 SCV004531656 uncertain significance Noonan syndrome 9 2023-10-04 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 392 of the SOS2 protein (p.Tyr392Cys). This variant is not present in population databases (gnomAD no frequency). 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: 426310). 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. 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.

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