ClinVar Miner

Submissions for variant NM_002834.5(PTPN11):c.557G>A (p.Arg186Gln)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002344744 SCV002647340 uncertain significance Cardiovascular phenotype 2022-01-05 criteria provided, single submitter clinical testing The p.R186Q variant (also known as c.557G>A), located in coding exon 5 of the PTPN11 gene, results from a G to A substitution at nucleotide position 557. The arginine at codon 186 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005002830 SCV005632282 uncertain significance Noonan syndrome 1; Juvenile myelomonocytic leukemia; Metachondromatosis; LEOPARD syndrome 1 2024-03-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV005096814 SCV005770427 uncertain significance RASopathy 2024-07-01 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 186 of the PTPN11 protein (p.Arg186Gln). This variant is present in population databases (rs764663951, gnomAD 0.0009%). 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: 1748415). 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 with a negative predictive value of 95%. 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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