ClinVar Miner

Submissions for variant NM_000834.5(GRIN2B):c.3812C>T (p.Ala1271Val)

gnomAD frequency: 0.00004  dbSNP: rs372379846
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235301 SCV000292823 likely benign not provided 2020-03-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003765470 SCV004605948 uncertain significance Intellectual disability, autosomal dominant 6; Developmental and epileptic encephalopathy, 27 2024-09-24 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1271 of the GRIN2B protein (p.Ala1271Val). This variant is present in population databases (rs372379846, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with GRIN2B-related conditions. ClinVar contains an entry for this variant (Variation ID: 245739). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt GRIN2B protein function with a negative predictive value of 95%. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004701331 SCV005204478 uncertain significance not specified 2024-06-11 criteria provided, single submitter clinical testing Variant summary: GRIN2B c.3812C>T (p.Ala1271Val) results in a non-conservative amino acid change located in the Glutamate [NMDA] receptor, epsilon subunit, C-terminal domain (IPR018884) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 251438 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3812C>T in individuals affected with Mental Retardation, Autosomal Dominant 6 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 245739). Based on the evidence outlined above, the variant was classified as uncertain significance.

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