ClinVar Miner

Submissions for variant NM_002834.5(PTPN11):c.1282G>T (p.Val428Leu)

dbSNP: rs397507536
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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 RCV001056808 SCV001221272 pathogenic RASopathy 2022-09-07 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 428 of the PTPN11 protein (p.Val428Leu). For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 852241). This missense change has been observed in individual(s) with clinical features of a RASopathy disorder (PMID: 24451042; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency).
GeneDx RCV001788413 SCV002030909 likely pathogenic not provided 2023-07-07 criteria provided, single submitter clinical testing Not observed in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30355600, 29493581, 24451042)
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV003514461 SCV004244518 likely pathogenic Noonan syndrome 1 2023-11-28 criteria provided, single submitter clinical testing PS4_Supporting, PM2, PM5_Supporting, PP2, PP3
Fulgent Genetics, Fulgent Genetics RCV005012502 SCV005632299 likely pathogenic Noonan syndrome 1; Juvenile myelomonocytic leukemia; Metachondromatosis; LEOPARD syndrome 1 2024-02-15 criteria provided, single submitter clinical testing

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