Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000306612 | SCV000343331 | uncertain significance | not provided | 2016-07-21 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000654964 | SCV000776874 | uncertain significance | RASopathy | 2021-10-21 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with tyrosine at codon 443 of the PTPN11 protein (p.His443Tyr). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is present in population databases (rs779236638, ExAC 0.002%). 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). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 | 2020-10-20 | 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, |
RCV002487262 | SCV002776035 | uncertain significance | Noonan syndrome 1; Juvenile myelomonocytic leukemia; Metachondromatosis; LEOPARD syndrome 1 | 2021-12-08 | criteria provided, single submitter | clinical testing |