Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001327153 | SCV001518215 | uncertain significance | Landau-Kleffner syndrome | 2021-12-08 | 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 GRIN2A protein function. ClinVar contains an entry for this variant (Variation ID: 1026673). This variant has not been reported in the literature in individuals affected with GRIN2A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 1412 of the GRIN2A protein (p.Cys1412Ser). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003331117 | SCV004037625 | uncertain significance | not specified | 2023-08-28 | criteria provided, single submitter | clinical testing | Variant summary: GRIN2A c.4235G>C (p.Cys1412Ser) results in a non-conservative amino acid change located in the Glutamate [NMDA] receptor, epsilon subunit, C-terminal domain (IPR018884) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 251178 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.4235G>C in individuals affected with Epilepsy, Focal, With Speech Disorder And With Or Without Mental Retardation and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |