Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV001785406 | SCV002026459 | likely pathogenic | Landau-Kleffner syndrome | 2019-01-01 | criteria provided, single submitter | research | |
Labcorp Genetics |
RCV001785406 | SCV004296393 | pathogenic | Landau-Kleffner syndrome | 2023-07-25 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with Landau-Kleffner syndrome (PMID: 23933820). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 694 of the GRIN2A protein (p.Ile694Thr). ClinVar contains an entry for this variant (Variation ID: 1325869). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects GRIN2A function (PMID: 27839871). 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. |