Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Biesecker Lab/Clinical Genomics Section, |
RCV000171996 | SCV000054756 | uncertain significance | not provided | 2013-06-24 | criteria provided, single submitter | research | |
| Laboratory for Molecular Medicine, |
RCV000038731 | SCV000062409 | uncertain significance | not specified | 2012-04-11 | criteria provided, single submitter | clinical testing | The Val491Glu variant (LDB3) has not been reported in the literature nor previou sly identified by our laboratory. Computational analyses (biochemical amino aci d properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Val 491Glu variant may impact the protein, though this information is not predictive enough to determine pathogenicity. This variant has been identified in 0.03% (1 /3738) of African American chromosomes from a broad population by the NHLBI Exom e Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs139709036). In summary, additional information is needed to fully assess the clinical signific ance of the Val491Glu variant. |
| Invitae | RCV001345111 | SCV001539211 | uncertain significance | Myofibrillar myopathy 4 | 2023-12-06 | 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.*17193T>A in the primary transcript. This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 491 of the LDB3 protein (p.Val491Glu). This variant is present in population databases (rs139709036, gnomAD 0.01%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 24503780, 27532257). 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 | RCV002390162 | SCV002697025 | uncertain significance | Cardiovascular phenotype | 2021-02-21 | criteria provided, single submitter | clinical testing | The p.V491E variant (also known as c.1472T>A), located in coding exon 9 of the LDB3 gene, results from a T to A substitution at nucleotide position 1472. The valine at codon 491 is replaced by glutamic acid, an amino acid with dissimilar properties. This variant has been detected in the homozygous state in an individual with pediatric-onset dilated cardiomyopathy who also had additional variants in LDB3 in addition to variants in other cardiac-related genes (Pugh TJ et al. Genet Med, 2014 Aug;16:601-8; Walsh R et al. Genet Med, 2017 02;19:192-203), and has also been detected in an exome cohort (referred to as c.1142T>A, p.V381E); however, details were limited (Ng D et al. Circ Cardiovasc Genet, 2013 Aug;6:337-46). This amino acid position is well 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, |
RCV002483000 | SCV002792201 | uncertain significance | Dilated cardiomyopathy 1C; Myofibrillar myopathy 4 | 2021-07-15 | criteria provided, single submitter | clinical testing |