ClinVar Miner

Submissions for variant NM_006939.4(SOS2):c.3644C>G (p.Thr1215Ser)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001348666 SCV001542975 uncertain significance Noonan syndrome 9 2020-08-14 criteria provided, single submitter clinical testing This sequence change replaces threonine with serine at codon 1215 of the SOS2 protein (p.Thr1215Ser). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and serine. This variant is present in population databases (rs773877975, ExAC 0.04%). This variant has not been reported in the literature in individuals with SOS2-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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