Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000079441 | SCV000111320 | uncertain significance | not provided | 2013-06-10 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000706758 | SCV000835827 | uncertain significance | Myofibrillar myopathy 4 | 2023-07-26 | 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. This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 54 of the LDB3 protein (p.Gly54Ser). This variant is present in population databases (rs201786090, gnomAD 0.005%). This missense change has been observed in individual(s) with hypertrophic or dilated cardiomyopathy (PMID: 24730657, 31983221, 32880476). ClinVar contains an entry for this variant (Variation ID: 93526). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. |
Ambry Genetics | RCV002390232 | SCV002703123 | uncertain significance | Cardiovascular phenotype | 2021-11-09 | criteria provided, single submitter | clinical testing | The p.G54S variant (also known as c.160G>A), located in coding exon 2 of the LDB3 gene, results from a G to A substitution at nucleotide position 160. The glycine at codon 54 is replaced by serine, an amino acid with similar properties. This variant was reported in an individual with severe hypertrophic cardiomyopathy (HCM) and in two dilated cardiomyopathy (DCM) cases with limited details (Fratev F et al. J Chem Inf Model, 2014 May;54:1524-36; Mazzarotto F et al. Circulation, 2020 02;141:387-398; Verdonschot JAJ et al. Circ Genom Precis Med, 2020 10;13:476-487). This amino acid position is highly 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. |
Diagnostic Laboratory, |
RCV000079441 | SCV001739864 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000079441 | SCV001954905 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000079441 | SCV001968029 | uncertain significance | not provided | no assertion criteria provided | clinical testing |