Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000033523 | SCV000057428 | likely benign | not provided | 2020-11-02 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000763793 | SCV000894707 | uncertain significance | Noonan syndrome 1; Juvenile myelomonocytic leukemia; Metachondromatosis; LEOPARD syndrome 1 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003539767 | SCV004305892 | uncertain significance | RASopathy | 2023-12-29 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 350 of the PTPN11 protein (p.Ser350Ala). This variant is present in population databases (rs146571700, gnomAD 0.003%). 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: 40540). 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 with a positive 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. |
Ambry Genetics | RCV004018712 | SCV004934876 | uncertain significance | Cardiovascular phenotype | 2020-01-23 | criteria provided, single submitter | clinical testing | The c.1048T>G (p.S350A) alteration is located in exon 9 (coding exon 9) of the PTPN11 gene. This alteration results from a T to G substitution at nucleotide position 1048, causing the serine (S) at amino acid position 350 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |