ClinVar Miner

Submissions for variant NM_000836.4(GRIN2D):c.2041A>G (p.Met681Val)

dbSNP: rs1555893359
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV001311541 SCV001501748 likely pathogenic not provided 2020-10-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001311541 SCV002188921 pathogenic not provided 2021-06-24 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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 expected to disrupt GRIN2D protein function. This variant has been observed in individual(s) with clinical features of developmental and epileptic encephalopathy (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 1013174). This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with valine at codon 681 of the GRIN2D protein (p.Met681Val). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and valine.
3billion RCV005253793 SCV005905649 likely pathogenic Developmental and epileptic encephalopathy, 46 2023-09-01 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. Predicted Consequence/Location: Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product [3Cnet: 0.97 (>=0.6, sensitivity 0.72 and precision 0.9)]. Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV001013174). A different missense change at the same codon (p.Met681Ile) has been reported to be associated with GRIN2D related disorder (ClinVar ID: VCV000599388 /PMID: 30280376). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.

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