ClinVar Miner

Submissions for variant NM_001368067.1(LDB3):c.772G>A (p.Glu258Lys)

dbSNP: rs868365512
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000492960 SCV000582039 uncertain significance not provided 2017-05-09 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the LDB3 gene. The E305K variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The E305K 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. Additionally, this substitution occurs at a position that is conserved across species. Furthermore, in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, the E305K variant occurs in an alternate transcript of the LDB3 gene, and no nearby missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with an LDB3-related disorder (Stenson et al., 2014).
Invitae RCV001856962 SCV002149434 uncertain significance Myofibrillar myopathy 4 2023-02-18 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 258 of the LDB3 protein (p.Glu258Lys). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with LDB3-related conditions. ClinVar contains an entry for this variant (Variation ID: 429461). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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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