ClinVar Miner

Submissions for variant NM_000834.4(GRIN2B):c.3993G>A (p.Met1331Ile) (rs200035225)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000429224 SCV000510636 uncertain significance not provided 2017-02-06 criteria provided, single submitter clinical testing Converted during submission to Uncertain significance.
GeneDx RCV000605961 SCV000726889 likely benign not specified 2018-01-25 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000720440 SCV000851317 likely benign History of neurodevelopmental disorder 2017-08-31 criteria provided, single submitter clinical testing In silico models in agreement (benign);Subpopulation frequency in support of benign classification
Invitae RCV000805212 SCV000945160 uncertain significance Mental retardation, autosomal dominant 6; Epileptic encephalopathy, early infantile, 27 2018-09-02 criteria provided, single submitter clinical testing This sequence change replaces methionine with isoleucine at codon 1331 of the GRIN2B protein (p.Met1331Ile). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is present in population databases (rs200035225, ExAC 0.009%). This variant has been observed in an individual with mild to moderate ID and/or seizures (PMID: 27818011). ClinVar contains an entry for this variant (Variation ID: 376804). 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 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.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000429224 SCV001148648 uncertain significance not provided 2018-11-01 criteria provided, single submitter clinical testing

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