ClinVar Miner

Submissions for variant NM_002834.5(PTPN11):c.846C>G (p.Ile282Met) (rs397507530)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000033506 SCV000057411 pathogenic not provided 2021-05-25 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 31560489, 26817465, 25742478, 21934682, 23917401)
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000037661 SCV000061323 likely pathogenic Noonan syndrome 2018-12-21 criteria provided, single submitter clinical testing The p.Ile282Met variant in PTPN11 has been reported in 3 individuals with clinic al features of Noonan syndrome and was inherited from an affected parent in one of these cases (Atik 2016, Klapecki 2005, LMM unpublished data). This variant wa s absent from large population studies. It has been reported in ClinVar (Variat ion ID 40526) and has been reported as a somatic variant in a glioblastoma (Frat tini 2013). Computational prediction tools and conservation analysis suggest th at this variant may impact the protein, though this information is not predictiv e enough to determine pathogenicity. Furthermore, another variant at this positi on (p.Ile282Val) has been reported in multiple individuals with clinical feature s of Noonan syndrome and is classified as pathogenic by our laboratory and in Cl inVar (Variation ID 40525). In summary, although additional studies are required to fully establish its clinical significance, the p.Ile282Met variant is likely pathogenic for autosomal dominant Noonan syndrome. ACMG/AMP criteria applied: P M2, PM5, PP3, PS4_Supporting.
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV001027860 SCV001190494 likely pathogenic Noonan syndrome 1 2019-12-18 criteria provided, single submitter research ACMG codes: PS4M, PM2, PP3, PP5
Service de Génétique Moléculaire,Hôpital Robert Debré RCV000037661 SCV001438413 likely pathogenic Noonan syndrome no assertion criteria provided clinical testing
Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Peking Union Medical College Hospital RCV001027860 SCV001482357 pathogenic Noonan syndrome 1 2019-05-31 no assertion criteria provided research

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