Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Institute of Human Genetics, |
RCV001706919 | SCV001934504 | uncertain significance | Developmental and epileptic encephalopathy, 27 | 2021-03-29 | criteria provided, single submitter | clinical testing | Despite strong evidence for its pathogenicity, this variant has to be classified as of unknown significance, according to the ACMG-criteria (Richards et al., 2015) |
| Labcorp Genetics |
RCV003771861 | SCV004589523 | uncertain significance | Intellectual disability, autosomal dominant 6; Developmental and epileptic encephalopathy, 27 | 2023-02-18 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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 not expected to disrupt GRIN2B protein function. ClinVar contains an entry for this variant (Variation ID: 1285562). This missense change has been observed in individual(s) with Lennox-Gastaut syndrome (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 240 of the GRIN2B protein (p.Ile240Val). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004526140 | SCV005040425 | uncertain significance | not specified | 2024-03-04 | criteria provided, single submitter | clinical testing | Variant summary: GRIN2B c.718A>G (p.Ile240Val) results in a conservative amino acid change located in the Receptor, ligand binding region (IPR001828) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 251160 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.718A>G in individuals affected with Mental Retardation, Autosomal Dominant 6 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1285562). Based on the evidence outlined above, the variant was classified as uncertain significance. |