Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000187643 | SCV000241240 | pathogenic | not provided | 2019-09-19 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a loss of normal protein function (Swanger et al., 2016, Gao et al., 2017; Addis et al., 2017); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 23933820, 25046240, 28182669, 27839871, 28242877, 28170084) |
Ce |
RCV000187643 | SCV001500060 | pathogenic | not provided | 2020-12-01 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics, |
RCV001781550 | SCV002026149 | likely pathogenic | Landau-Kleffner syndrome | 2019-01-01 | criteria provided, single submitter | research | |
Invitae | RCV001781550 | SCV002229265 | pathogenic | Landau-Kleffner syndrome | 2023-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 731 of the GRIN2A protein (p.Asp731Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of GRIN2A-related conditions (PMID: 23933820, 28182669). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 205657). 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. Experimental studies have shown that this missense change affects GRIN2A function (PMID: 28182669). For these reasons, this variant has been classified as Pathogenic. |