ClinVar Miner

Submissions for variant NM_002834.5(PTPN11):c.1472C>A (p.Pro491His) (rs397507540)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000033537 SCV000057442 pathogenic not provided 2017-12-04 criteria provided, single submitter clinical testing The P491H variant has been published as a pathogenic variant in association with Noonan syndrome (Bertola et at., 2006). The P491H variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P491H variant 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. In silico analysis predicts this variant is probably damaging to the protein structure/function. Pathogenic missense variants in this residue (P491S, P491T, P491L) have been reported in the Human Gene Mutation Database and observed at GeneDx in association with a RASopathy (Stenson et al., 2014). In summary, this variant is pathogenic.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000037617 SCV000061279 pathogenic Noonan syndrome 2015-09-29 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
Blueprint Genetics RCV000033537 SCV000927247 pathogenic not provided 2017-05-04 criteria provided, single submitter clinical testing

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