ClinVar

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Asn58 amino acid residue in PTPN11. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12634870, 15001945, 15956085, 16263833, 16358218, 19125092, 20954246, 21204800, 22190897, 23321623, 23624134, 23756559, 25914815). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: 40488). A different variant (c.174C>G) giving rise to the same protein effect has been determined to be pathogenic (PMID: 12634870, 15001945, 15956085, 16263833, 16358218, 19125092, 20954246, 21204800, 22190897, 23321623, 23624134, 23756559, 25914815). This suggests that this variant is also likely to be causative of disease. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 58 of the PTPN11 protein (p.Asn58Lys).