Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000870799 | SCV001012342 | uncertain significance | Myofibrillar myopathy 4 | 2024-01-16 | 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.321+1361C>A in the primary transcript. This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 135 of the LDB3 protein (p.Thr135Asn). This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 702008). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. |
| Gene |
RCV001552342 | SCV001773011 | uncertain significance | not provided | 2019-04-18 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function |
| Ambry Genetics | RCV002320017 | SCV002630148 | uncertain significance | Cardiovascular phenotype | 2022-03-21 | criteria provided, single submitter | clinical testing | The p.T135N variant (also known as c.404C>A), located in coding exon 4 of the LDB3 gene, results from a C to A substitution at nucleotide position 404. The threonine at codon 135 is replaced by asparagine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and asparagine is the reference amino acid in other 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. |