Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001246128 | SCV001419467 | uncertain significance | Myofibrillar myopathy 4 | 2023-08-09 | criteria provided, single submitter | clinical testing | 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. The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.*17268G>A in the primary transcript. This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 516 of the LDB3 protein (p.Arg516Gln). This variant is present in population databases (rs762985970, gnomAD 0.003%). 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001260421 | SCV001437413 | uncertain significance | not specified | 2020-09-08 | criteria provided, single submitter | clinical testing | Variant summary: LDB3 c.1547G>A (p.Arg516Gln) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 250678 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1547G>A in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, citing the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Ambry Genetics | RCV002402783 | SCV002709388 | uncertain significance | Cardiovascular phenotype | 2022-09-12 | criteria provided, single submitter | clinical testing | The p.R516Q variant (also known as c.1547G>A), located in coding exon 9 of the LDB3 gene, results from a G to A substitution at nucleotide position 1547. The arginine at codon 516 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |