Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV000488193 | SCV000575611 | pathogenic | not provided | 2019-11-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000488193 | SCV001811766 | pathogenic | not provided | 2021-05-12 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate altered NMDA receptor function (Fry et al., 2018); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 29365063) |
Invitae | RCV002526005 | SCV003460786 | pathogenic | Intellectual disability, autosomal dominant 8 | 2022-07-27 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects GRIN1 function (PMID: 29365063). 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 GRIN1 protein function. ClinVar contains an entry for this variant (Variation ID: 425473). This missense change has been observed in individual(s) with autosomal dominant GRIN1-related conditions (PMID: 29365063). 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 arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 659 of the GRIN1 protein (p.Arg659Trp). |