Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000617623 | SCV000737303 | uncertain significance | Cardiovascular phenotype | 2017-08-07 | criteria provided, single submitter | clinical testing | The p.E157K variant (also known as c.469G>A), located in coding exon 4 of the LDB3 gene, results from a G to A substitution at nucleotide position 469. The glutamic acid at codon 157 is replaced by lysine, an amino acid with 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. |
Invitae | RCV001398331 | SCV001600100 | uncertain significance | Myofibrillar myopathy 4 | 2023-10-04 | 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+1426G>A in the primary transcript. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 157 of the LDB3 protein (p.Glu157Lys). This variant is present in population databases (rs770678454, gnomAD 0.003%). 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: 519179). 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. |