ClinVar Miner

Submissions for variant NM_002834.5(PTPN11):c.1498C>G (p.Gln500Glu)

dbSNP: rs2038714548
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001961060 SCV002239870 uncertain significance RASopathy 2021-05-07 criteria provided, single submitter clinical testing This variant has been observed in individual(s) with clinical features of PTPN11-related conditions (Invitae). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PTPN11 protein function. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with glutamic acid at codon 500 of the PTPN11 protein (p.Gln500Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid.
AiLife Diagnostics, AiLife Diagnostics RCV002224124 SCV002503019 uncertain significance not provided 2021-11-20 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002484823 SCV002782332 uncertain significance Noonan syndrome 1; Juvenile myelomonocytic leukemia; Metachondromatosis; LEOPARD syndrome 1 2024-02-27 criteria provided, single submitter clinical testing
GeneDx RCV002224124 SCV005375879 uncertain significance not provided 2023-11-13 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously reported as a pathogenic or benign germline variant to our knowledge; This variant is associated with the following publications: (PMID: 29493581, 37445722)

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