ClinVar Miner

Submissions for variant NM_006912.6(RIT1):c.334C>T (p.Arg112Cys) (rs375724784)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000469107 SCV000541754 uncertain significance Noonan syndrome 8 2018-08-30 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 112 of the RIT1 protein (p.Arg112Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs375724784, ExAC 0.02%) but has not been reported in the literature in the germline of individuals with a RIT1-related disease. 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 disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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