Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001370242 | SCV001566710 | uncertain significance | Intellectual disability, autosomal dominant 8 | 2020-05-04 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with GRIN1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with serine at codon 112 of the GRIN1 protein (p.Gly112Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003331136 | SCV004037829 | uncertain significance | not specified | 2023-08-31 | criteria provided, single submitter | clinical testing | Variant summary: GRIN1 c.334G>A (p.Gly112Ser) results in a non-conservative amino acid change located in the ligand binding region (IPR001828) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6.6e-06 in 150964 control chromosomes (gnomAD v3.1, genomes dataset). 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.334G>A in individuals affected with Neurodevelopmental Disorder With Or Without Hyperkinetic Movements And Seizures, Autosomal Dominant 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. |