ClinVar Miner

Submissions for variant NM_007078.3(LDB3):c.1774G>C (p.Glu592Gln) (rs727504944)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000156345 SCV000206063 uncertain significance not specified 2014-08-21 criteria provided, single submitter clinical testing The Glu592Gln variant in LDB3 has not been previously reported in individuals wi th cardiomyopathy or in large population studies. Computational prediction tools and conservation analysis do not provide strong evidence for or against an impa ct the protein. In summary, the clinical significance of the Glu592Gln variant i s uncertain.
GeneDx RCV000767127 SCV000236019 uncertain significance not provided 2011-10-24 criteria provided, single submitter clinical testing p.Glu592Gln (GAG>CAG): c.1774 G>C in the LDB3 gene (NM_007078.2). The Glu592Gln variant in the LDB3 gene has not been reported previously as a disease-causing mutation nor as a benign polymorphism, to our knowledge. Glu592Gln results in a non-conservative amino acid substitution of a negatively charged Glutamic acid with a neutral, polar Glutamine at a residue that is conserved across species. In silico analysis predicts Glu592Gln is probably damaging to the protein structure/function (Adzhubei et al. 2010; Schwarz et al. 2010). However, no disease-causing mutations have been reported in this region of the LDB3 gene to date. In summary, with the clinical and molecular information available at this time, we cannot unequivocally determine whether the Glu592Gln variant is a disease-causing mutation or a benign variant. The variant is found in DCM panel(s).
Invitae RCV000639878 SCV000761461 uncertain significance Myofibrillar myopathy, ZASP-related 2018-08-28 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glutamine at codon 592 of the LDB3 protein (p.Glu592Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine. The LDB3 gene has multiple clinically relevant isoforms. The p.Glu592Gln variant occurs in alternate transcript NM_007078.2, which corresponds to position c.*18687G>A in NM_001080116.1, the primary transcript listed in the Methods. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with LDB3-related disease. ClinVar contains an entry for this variant (Variation ID: 179553). 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: "Not Available; Align-GVGD: "Class C25"). 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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