Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002318264 | SCV000851563 | uncertain significance | Inborn genetic diseases | 2017-02-03 | criteria provided, single submitter | clinical testing | The c.1198-3C>A intronic variant results from a C to A substitution 3 nucleotides upstream from coding exon 9 in the GRIN1 gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice acceptor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001862085 | SCV002175829 | uncertain significance | Intellectual disability, autosomal dominant 8 | 2023-11-11 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 8 of the GRIN1 gene. It does not directly change the encoded amino acid sequence of the GRIN1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs200368768, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with GRIN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 590082). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |