ClinVar Miner

Submissions for variant NM_002834.4(PTPN11):c.1579C>T (p.Arg527Cys) (rs191525506)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Phosphorus, Inc. RCV000577961 SCV000679872 uncertain significance LEOPARD syndrome 1 2017-08-01 criteria provided, single submitter clinical testing
Phosphorus, Inc. RCV000578039 SCV000679873 uncertain significance Metachondromatosis 2017-08-01 criteria provided, single submitter clinical testing
Phosphorus, Inc. RCV000578115 SCV000679874 uncertain significance Noonan syndrome 1 2017-08-01 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV001091428 SCV001247476 uncertain significance not provided 2019-08-01 criteria provided, single submitter clinical testing
Invitae RCV001239106 SCV001411956 uncertain significance Rasopathy 2019-06-27 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 527 of the PTPN11 protein (p.Arg527Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs191525506, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with PTPN11-related conditions. ClinVar contains an entry for this variant (Variation ID: 488166). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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