ClinVar Miner

Submissions for variant NM_006939.4(SOS2):c.2315T>G (p.Phe772Cys)

gnomAD frequency: 0.00002  dbSNP: rs200715068
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001220096 SCV001392069 uncertain significance Noonan syndrome 9 2023-12-06 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 772 of the SOS2 protein (p.Phe772Cys). This variant is present in population databases (rs200715068, gnomAD 0.02%), and has an allele count higher than expected for a pathogenic variant. 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: 948773). 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 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.

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