ClinVar Miner

Submissions for variant NM_002834.5(PTPN11):c.1327C>T (p.His443Tyr)

gnomAD frequency: 0.00003  dbSNP: rs779236638
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000306612 SCV000343331 uncertain significance not provided 2016-07-21 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000654964 SCV000776874 uncertain significance RASopathy 2024-10-03 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 443 of the PTPN11 protein (p.His443Tyr). This variant is present in population databases (rs779236638, gnomAD 0.007%). 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: 289057). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt PTPN11 protein function with a negative predictive value of 80%. 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 RCV002379149 SCV002691596 uncertain significance Cardiovascular phenotype 2025-01-08 criteria provided, single submitter clinical testing The p.H443Y variant (also known as c.1327C>T), located in coding exon 11 of the PTPN11 gene, results from a C to T substitution at nucleotide position 1327. The histidine at codon 443 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is well 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.
Fulgent Genetics, Fulgent Genetics RCV002487262 SCV002776035 uncertain significance Noonan syndrome 1; Juvenile myelomonocytic leukemia; Metachondromatosis; LEOPARD syndrome 1 2021-12-08 criteria provided, single submitter clinical testing

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