Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular 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. |
| Gene |
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 4 | 2024-01-02 | criteria provided, single submitter | clinical testing | The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.*18687G>C in the primary transcript. This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 592 of the LDB3 protein (p.Glu592Gln). This variant is present in population databases (rs727504944, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with LDB3-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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 | RCV002399557 | SCV002714820 | uncertain significance | Cardiovascular phenotype | 2022-06-24 | criteria provided, single submitter | clinical testing | The p.E592Q variant (also known as c.1774G>C), located in coding exon 10 of the LDB3 gene, results from a G to C substitution at nucleotide position 1774. The glutamic acid at codon 592 is replaced by glutamine, an amino acid with highly similar properties. This variant was reported in a familial pacemaker cohort; however, clinical details were limited (Celestino-Soper PB et al. PLoS One, 2015 Dec;10:e0143588). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV002505175 | SCV002814537 | uncertain significance | Dilated cardiomyopathy 1C; Myofibrillar myopathy 4 | 2021-08-19 | criteria provided, single submitter | clinical testing |