ClinVar Miner

Submissions for variant NM_001134407.3(GRIN2A):c.1912G>A (p.Ala638Thr)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV005168725 SCV005800164 likely pathogenic Landau-Kleffner syndrome 2024-12-09 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 638 of the GRIN2A protein (p.Ala638Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GRIN2A-related conditions. This missense change has been observed in at least one individual who was not affected with GRIN2A-related conditions (internal data). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt GRIN2A protein function with a positive predictive value of 95%. This variant disrupts the p.Ala638 amino acid residue in GRIN2A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 38764027). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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