Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000801372 | SCV000941146 | uncertain significance | Myofibrillar myopathy 4 | 2023-08-21 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with LDB3-related conditions. 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 646981). This variant is present in population databases (rs775232208, gnomAD 0.01%). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 566 of the LDB3 protein (p.Met566Val). The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.*18609A>G in the primary transcript. |
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV000845315 | SCV000987357 | uncertain significance | Primary familial dilated cardiomyopathy | criteria provided, single submitter | clinical testing | ||
Laboratory for Molecular Medicine, |
RCV001449770 | SCV001653045 | uncertain significance | not specified | 2020-06-15 | criteria provided, single submitter | clinical testing | The p.Met566Val variant in LDB3 has not been previously reported in individuals with cardiomyopathy but has been identified in 0.01% (5/34590) of Latino and 0.004% (5/113736) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: none. |
Baylor Genetics | RCV003147552 | SCV003836243 | uncertain significance | Dilated cardiomyopathy 1C | 2022-02-10 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003372857 | SCV004095148 | uncertain significance | Cardiovascular phenotype | 2023-06-19 | criteria provided, single submitter | clinical testing | The p.M566V variant (also known as c.1696A>G), located in coding exon 10 of the LDB3 gene, results from an A to G substitution at nucleotide position 1696. The methionine at codon 566 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |