ClinVar Miner

Submissions for variant NM_000834.4(GRIN2B):c.4041C>A (p.Ser1347Arg) (rs769147604)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521371 SCV000621939 uncertain significance not provided 2017-10-31 criteria provided, single submitter clinical testing The S1347R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The S1347R variant is observed in 1/15,304 (0.007%) alleles from individuals of African background (Lek et al., 2016). The S1347R variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved, and Arginine is observed at this position in evolution. In silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina RCV000287107 SCV000377100 uncertain significance Intellectual Disability, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000798539 SCV000938160 uncertain significance Mental retardation, autosomal dominant 6; Epileptic encephalopathy, early infantile, 27 2018-09-11 criteria provided, single submitter clinical testing This sequence change replaces serine with arginine at codon 1347 of the GRIN2B protein (p.Ser1347Arg). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and arginine. This variant is present in population databases (rs769147604, ExAC 0.01%). This variant has not been reported in the literature in individuals with GRIN2B-related disease. ClinVar contains an entry for this variant (Variation ID: 307738). 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.

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