ClinVar Miner

Submissions for variant NM_000834.5(GRIN2B):c.1646C>G (p.Ala549Gly)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003782644 SCV004604413 uncertain significance Intellectual disability, autosomal dominant 6; Developmental and epileptic encephalopathy, 27 2023-12-21 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 549 of the GRIN2B protein (p.Ala549Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GRIN2B-related conditions. 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 GRIN2B protein function with a positive 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.
Ambry Genetics RCV004981017 SCV005592406 uncertain significance Inborn genetic diseases 2024-10-03 criteria provided, single submitter clinical testing The c.1646C>G (p.A549G) alteration is located in exon 7 (coding exon 6) of the GRIN2B gene. This alteration results from a C to G substitution at nucleotide position 1646, causing the alanine (A) at amino acid position 549 to be replaced by a glycine (G). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. This missense alteration is located in a region that has a low rate of benign missense variation (Lek, 2016; Firth, 2009). This alteration is predicted to be deleterious by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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