Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000639585 | SCV000761162 | pathogenic | Landau-Kleffner syndrome | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 558 of the GRIN2A protein (p.Trp558Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with epilepsy and GRIN2A-related disorders (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 532714). 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 GRIN2A protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |