ClinVar Miner

Submissions for variant NM_002834.5(PTPN11):c.1468G>A (p.Val490Ile)

gnomAD frequency: 0.00002  dbSNP: rs781083623
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000681133 SCV000808591 uncertain significance not provided 2023-09-25 criteria provided, single submitter clinical testing Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 26053092, 29493581)
Labcorp Genetics (formerly Invitae), Labcorp RCV001861893 SCV002278914 uncertain significance RASopathy 2023-10-23 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 490 of the PTPN11 protein (p.Val490Ile). This variant is present in population databases (rs781083623, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with PTPN11-related conditions. ClinVar contains an entry for this variant (Variation ID: 561751). 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 not expected to disrupt PTPN11 protein function. 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.
Ambry Genetics RCV002388191 SCV002702176 uncertain significance Cardiovascular phenotype 2019-04-08 criteria provided, single submitter clinical testing The p.V490I variant (also known as c.1468G>A), located in coding exon 13 of the PTPN11 gene, results from a G to A substitution at nucleotide position 1468. The valine at codon 490 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Service de Génétique Moléculaire, Hôpital Robert Debré RCV001261019 SCV001438416 uncertain significance Noonan syndrome no assertion criteria provided clinical testing

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