Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000624738 | SCV000740733 | pathogenic | Inborn genetic diseases | 2014-09-24 | criteria provided, single submitter | clinical testing | The c.1645A>C (p.S549R) alteration is located in exon 12 (coding exon 12) of the GRIN1 gene. This alteration results from a A to C substitution at nucleotide position 1645, causing the serine (S) at amino acid position 549 to be replaced by an arginine (R). The alteration is not observed in healthy cohorts:_x000D_ Based on data from the NHLBI Exome Sequencing Project (ESP), the GRIN1 c.1645A>C alteration was not observed among 6,227 individuals tested. Allele frequency data for this nucleotide position are not currently available from the 1000 Genomes Project and the alteration is not currently listed in the Database of Single Nucleotide Polymorphisms (dbSNP). The altered nucleotide is conserved throughout evolution:_x000D_ The c.1645A nucleotide is completely conserved in available vertebrate species._x000D_ The altered amino acid is conserved throughout evolution:_x000D_ The p.S549 amino acid is completely conserved in available vertebrate species. The alteration is predicted deleterious by in silico models:_x000D_ The p.S549R alteration is predicted to be probably damaging by Polyphen and deleterious by SIFT in silico analyses._x000D_ The alteration is predicted not to affect splicing by in silico models:_x000D_ Based on BDGP and ESEfinder splice site in silico tools, this alteration does not have any significant effect on the native acceptor/donor splice site; however, direct evidence is unavailable. Based on the available evidence, this alteration is classified as pathogenic. |
| 3billion, |
RCV003152721 | SCV003841550 | likely pathogenic | Intellectual disability, autosomal dominant 8 | 2023-02-23 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. The variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.70; 3Cnet: 0.82). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with GRIN1-related disorder (ClinVar ID: VCV000520575 / PMID: 27164704). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. |