ClinVar Miner

Submissions for variant NM_001099922.3(ALG13):c.2213A>G (p.Glu738Gly) (rs374174400)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000230246 SCV000285849 uncertain significance Epileptic encephalopathy, early infantile, 36 2019-12-24 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glycine at codon 738 of the ALG13 protein (p.Glu738Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is present in population databases (rs374174400, ExAC 0.01%). This variant has not been reported in the literature in individuals with ALG13-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; 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.
GeneDx RCV000523188 SCV000618113 uncertain significance not provided 2017-08-17 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ALG13 gene. The E738G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The E738G variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The E738G 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 that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants in nearby residues have not been reported in the Human Gene Mutation Database (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.

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