Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000532186 | SCV000651699 | likely pathogenic | Intellectual disability, autosomal dominant 8 | 2019-07-16 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with leucine at codon 818 of the GRIN1 protein (p.Met818Leu). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and leucine. This variant has been observed to be de novo in an individual with clinical features of GRIN1-related conditions (Invitae). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |