ClinVar Miner

Submissions for variant NM_002524.5(NRAS):c.71T>A (p.Ile24Asn) (rs869025573)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522652 SCV000617344 pathogenic not provided 2017-10-23 criteria provided, single submitter clinical testing The I24N variant has been reported previously as apparently de novo occurrences in association with Noonan syndrome (Runtuwene et al., 2011; Denayer et al., 2012). The variant is not observed in large population cohorts (Lek et al., 2016). I24N 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 conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, functional studies have shown I24N increases MAPK phosphorylation and activation (Runtuwene et al., 2011). In summary, we consider this variant to be pathogenic.
GeneReviews RCV000208553 SCV000264345 pathogenic Noonan syndrome 1 2016-02-25 no assertion criteria provided literature only

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