Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001945584 | SCV002196415 | uncertain significance | RASopathy | 2022-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 257 of the PTPN11 protein (p.Gln257Arg). 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. 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: 1422291). This variant has not been reported in the literature in individuals affected with PTPN11-related conditions. This variant is not present in population databases (gnomAD no frequency). |
Fulgent Genetics, |
RCV002503618 | SCV002814324 | uncertain significance | Noonan syndrome 1; Juvenile myelomonocytic leukemia; Metachondromatosis; LEOPARD syndrome 1 | 2022-02-04 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004656742 | SCV005155782 | uncertain significance | Cardiovascular phenotype | 2024-04-25 | criteria provided, single submitter | clinical testing | The p.Q257R variant (also known as c.770A>G), located in coding exon 7 of the PTPN11 gene, results from an A to G substitution at nucleotide position 770. The glutamine at codon 257 is replaced by arginine, 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 deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |