ClinVar Miner

Submissions for variant NM_002834.4(PTPN11):c.766C>A (p.Gln256Lys) (rs1391791847)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000680808 SCV000808253 likely pathogenic not provided 2018-08-14 criteria provided, single submitter clinical testing The Q256K variant has been published previously in association with Noonan syndrome (Binder et al., 2005). The variant is not observed in large population cohorts (Lek et al., 2016). Q256K is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. However, missense variants in the same residue (Q256R) and in nearby residues (E258D, C259S, L261F/H) have been reported in the Human Gene Mutation Database in association with Noonan syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein. In summary, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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