ClinVar Miner

Submissions for variant NM_006939.4(SOS2):c.1633C>T (p.Arg545Cys)

gnomAD frequency: 0.00001  dbSNP: rs148019428
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001991255 SCV002263698 uncertain significance Noonan syndrome 9 2024-01-25 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 545 of the SOS2 protein (p.Arg545Cys). This variant is present in population databases (rs148019428, gnomAD 0.01%). 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: 1480273). 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 95%. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003987952 SCV004804280 uncertain significance not specified 2024-01-08 criteria provided, single submitter clinical testing
GeneDx RCV004770337 SCV005378407 uncertain significance not provided 2023-11-21 criteria provided, single submitter clinical testing 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

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