ClinVar Miner

Submissions for variant NM_001134407.3(GRIN2A):c.1510C>T (p.Arg504Trp)

gnomAD frequency: 0.00003  dbSNP: rs1360906241
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000806105 SCV000946086 pathogenic Landau-Kleffner syndrome 2024-02-17 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 504 of the GRIN2A protein (p.Arg504Trp). This variant is present in population databases (no rsID available, gnomAD no frequency). This missense change has been observed in individuals with clinical features of GRIN2A-related conditions (PMID: 23933820; Invitae). ClinVar contains an entry for this variant (Variation ID: 650867). 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%. Experimental studies have shown that this missense change affects GRIN2A function (PMID: 27839871). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV002245677 SCV002512894 pathogenic not provided 2022-04-29 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect showing impaired GRIN2A protein function through reduced synaptic and non-synaptic charge transfer, as well as reduced glutamate potency, glycine potency and amplitude peak (Swanger et al., 2016); Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25498981, 27839871, 24576404, 33240831, 28488083, 25921602, 32144935, 26763624, 23933820)
Mendelics RCV000806105 SCV002516518 pathogenic Landau-Kleffner syndrome 2022-05-04 criteria provided, single submitter clinical testing

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