ClinVar Miner

Submissions for variant NM_001134407.3(GRIN2A):c.2197G>A (p.Ala733Thr) (rs796052550)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187644 SCV000241241 likely pathogenic not provided 2014-04-23 criteria provided, single submitter clinical testing p.Ala733Thr (GCA>ACA): c.2197 G>A in exon 12 of the GRIN2A gene (NM_000833.3). The A733T variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position in the extracellular domain that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.The variant is found in EPILEPSY panel(s).
Invitae RCV000639588 SCV000761165 uncertain significance Epilepsy, focal, with speech disorder and with or without mental retardation 2017-11-27 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 733 of the GRIN2A protein (p.Ala733Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with GRIN2A-related disease. ClinVar contains an entry for this variant (Variation ID: 205658). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Center of Genomic medicine, Geneva,University Hospital of Geneva RCV000639588 SCV000840408 uncertain significance Epilepsy, focal, with speech disorder and with or without mental retardation 2018-01-04 criteria provided, single submitter clinical testing

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