ClinVar Miner

Submissions for variant NM_002834.4(PTPN11):c.226G>A (p.Glu76Lys) (rs121918464)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212892 SCV000057381 pathogenic not provided 2013-02-05 criteria provided, single submitter clinical testing The E76K missense change not been published as a germline mutation associated with a hereditary disorder or benign polymorphism to our knowledge. However, E76K has been reported previously in the literature in association with somatic hematologic malignancies (Tartaglia et al., 2006). A different missense mutation this codon (E76D) has been reported previously in association with Noonan syndrome (Tartaglia et al., 2001 and Tartaglia et al., 2006). It lies in the N-SH2 domain of the gene, which is a hot spot for Noonan syndrome mutations. The presence of this mutation is consistent with a diagnosis of Noonan syndrome. The variant is found in NOONAN panel(s).
Blueprint Genetics RCV000212892 SCV000927623 pathogenic not provided 2018-04-09 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000014264 SCV001365520 pathogenic Juvenile myelomonocytic leukemia 2019-06-21 criteria provided, single submitter clinical testing The p.Glu76Lys variant in PTPN11 is an established pathogenic variant that has been identified as a somatic change in >40 individuals with JMML (Tartaglia 2003, Loh 2004, Kratz 2005, Tartaglia 2005, Aoki 2008, Yoshida 2009) and is absent from large population studies. In vitro and in vivo functional studies show that this variant has a strong gain of function impact (Tartaglia 2003, Loh 2004, Xu 2011, Yu 2013, Chang 2016, Dong 2016). Several other variants involving this codon have been identified in individuals with Noonan syndrome and/or hematological malignancies. In summary, this variant meets criteria to be classified as pathogenic for JMML.
OMIM RCV000014264 SCV000034513 pathogenic Juvenile myelomonocytic leukemia 2003-06-01 no assertion criteria provided literature only
Baylor Genetics RCV000033476 SCV000196661 pathogenic Rasopathy no assertion criteria provided clinical testing Variant classified using ACMG guidelines
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000156974 SCV000206696 pathogenic Noonan syndrome 2013-05-10 no assertion criteria provided clinical testing
Database of Curated Mutations (DoCM) RCV000422851 SCV000507244 likely pathogenic Multiple myeloma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433549 SCV000507245 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439757 SCV000507246 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422541 SCV000507247 likely pathogenic Neuroblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432364 SCV000507248 likely pathogenic Astrocytoma 2016-05-31 no assertion criteria provided literature only

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