Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV000191091 | SCV000245488 | likely pathogenic | Intellectual disability, autosomal dominant 8 | 2014-10-21 | criteria provided, single submitter | clinical testing | Likely pathogenicity based on finding it twice in our laboratory de novo: in a 24-year-old female with absent speech, autism, intellectual disability, mild unilateral conductive hearing loss, spasticity, joint laxity, failure to thrive, gastroesophageal disorder, strabismus, myopia, mild mitral valve prolapse, intermittent episodes of syncope, and scoliosis; in a 7-year-old male with absent speech, regression, intellectual disability, congenital hypotonia, movement disorder, short stature |
Gene |
RCV000479068 | SCV000569832 | pathogenic | not provided | 2023-01-21 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect: loss of NMDA receptor function (Lemke et al., 2016; Chen et al., 2017); Not observed at 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: 27164704, 26633545, 28228639, 31487502, 31429998) |
Ambry Genetics | RCV000622498 | SCV000742522 | likely pathogenic | Inborn genetic diseases | 2017-05-15 | criteria provided, single submitter | clinical testing | |
Equipe Genetique des Anomalies du Developpement, |
RCV001526577 | SCV001737004 | pathogenic | Seizure | criteria provided, single submitter | research | ||
Greenwood Genetic Center Diagnostic Laboratories, |
RCV000479068 | SCV002051694 | pathogenic | not provided | 2021-01-19 | criteria provided, single submitter | clinical testing | PS3, PP2, PP3, PM1, PM2, PS4_Moderate |
Invitae | RCV000191091 | SCV002240115 | pathogenic | Intellectual disability, autosomal dominant 8 | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 620 of the GRIN1 protein (p.Gly620Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of autosomal dominant GRIN1-related conditions (PMID: 28228639, 34884460). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 209159). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GRIN1 protein function. Experimental studies have shown that this missense change affects GRIN1 function (PMID: 28228639, 31429998). For these reasons, this variant has been classified as Pathogenic. |
Ce |
RCV000479068 | SCV002498081 | pathogenic | not provided | 2022-03-01 | criteria provided, single submitter | clinical testing | GRIN1: PS2, PM1, PM2, PP2, PP3, PS3:Supporting |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000191091 | SCV002511789 | pathogenic | Intellectual disability, autosomal dominant 8 | 2022-04-16 | criteria provided, single submitter | clinical testing | Variant summary: GRIN1 c.1858G>C (p.Gly620Arg) results in a non-conservative amino acid change located in the Ionotropic glutamate receptor domain (IPR001320) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 244402 control chromosomes. c.1858G>C has been reported in the literature as a de-novo variant in multiple individuals affected with features of Autosomal Dominant Neurodevelopmental Disorder With Or Without Hyperkinetic Movements And Seizures (example, Chen_2017, Lemke_2016, Costain_2019, Li_2019, Santos-Gomez_2021). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function reporting a reduction in N-methyl-D-aspartate (NMDAR) receptor trafficking, expression and function (example, Chen_2017). Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
OMIM | RCV000191091 | SCV000678284 | pathogenic | Intellectual disability, autosomal dominant 8 | 2022-03-28 | no assertion criteria provided | literature only |